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Pan Vascular Medicine pp 887–912Cite as

Coronary Artery Disease and Endothelial Function

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Abstract

The endothelium is not only a single-cell layered mechanical barrier between the blood and vessel wall, but regulates various important functions of the vasculature such as vaso-motion and, therefore, blood flow regulation, hemostasis, and wall proliferation processes. Atherosclerosis is associated with an impairment of these endothelial functions, favoring myocardial ischemia and progression of the disease [1]. Thus, the endothelium plays a central role in the process of atherosclerotic disease [2,3].

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References

  1. Fuster V, Badimon L, Badimon JJ, Chesebro JH (1992) The pathogenesis of coronary artery disease and the acute coronary syndrome (2). N Engl J Med 326:310–318

    CAS  PubMed  Google Scholar 

  2. Anderson TJ (1999) Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol 34:631–637

    CAS  PubMed  Google Scholar 

  3. Britten MB, Zeiher AM, Schächinger V (1999) Clinical importance of coronary endothelial vasodilator dysfunction and therapeutic options. J Intern Med 245:315–328

    CAS  PubMed  Google Scholar 

  4. Vane JR, Anggard EE, Bolting RM (1990) Regulatory functions of the vascular endothelium. N Engl J Med 323:27–36

    CAS  PubMed  Google Scholar 

  5. Fleming I, Busse R (1999) NO: the primary EDRE J Mol Cell Cardiol 31:5–14

    CAS  Google Scholar 

  6. Bassenge E, Busse R (1988) Endothelial modulation of coronary tone. Prog Cardiovasc Dis 30:349–380

    CAS  PubMed  Google Scholar 

  7. Nishimura RA, Lerman A, Chesebro IH, Ilstrup DM, Hodge DO, Higano ST et al (1995) Epicardial vasomotor responses to acetylcholine are not predicted by coronary atherosclerosis as assessed by intracoronary ultrasound. J Am Coll Cardiol 26:41–49

    CAS  PubMed  Google Scholar 

  8. Moncada S, Hill JA (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012

    CAS  PubMed  Google Scholar 

  9. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399:601–605

    CAS  PubMed  Google Scholar 

  10. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA et al (1995) Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 91:2488–2496

    CAS  PubMed  Google Scholar 

  11. Vink H, Constantinescu AA, Spaan JAE (2000) Oxidized lipoproteins degrade the endothelial surface layer: implications of platelet-endothelial cell adhesion. Circulation 101:1500–1502

    CAS  PubMed  Google Scholar 

  12. Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87:840–844

    CAS  PubMed  Google Scholar 

  13. Vinten-Johansen J (2000) Physiological effects of peroxynitrite: potential products of the environment. Circ Res 87:170–172

    CAS  PubMed  Google Scholar 

  14. Guzik TJ, West NE, Black E, McDonald D, Ratnatunga C, Pillai R et al (2000) Vascular superoxide production by NAD(P)H oxidase: association with endothelial dysfunction and clinical risk factors. Circ Res 86:E85–E90

    Google Scholar 

  15. Ohara Y, Peterson TE, Harrison DG (1993) Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 91:2546–2551

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Busse R, Fleming I (1996) Endothelial dysfunction in atherosclerosis. J Vasc Res 33:181–194

    CAS  PubMed  Google Scholar 

  17. Griendling KK, Sorescu D, Lassegue B, Ushio-Fukai M (2000) Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol 20:2175–2183

    CAS  PubMed  Google Scholar 

  18. Bloodsworth A, O’Donnell VB, Freeman BA (2000) Nitric oxide regulation of free radical- and enzyme-mediated lipid and lipoprotein oxidation. Arterioscler Thromb Vasc Biol 20:1707–1715

    CAS  PubMed  Google Scholar 

  19. Griendling KK, Harrison DG (1999) Dual role of reactive oxygen species in vascular growth (editorial). Circ Res 85:562–563

    CAS  PubMed  Google Scholar 

  20. Channon KM, Qian H, George SE (2000) Nitric oxide synthase in atherosclerosis and vascular injury: insights from experimental gene therapy. Arterioscler Thromb Vasc Biol 20:1873–1881

    CAS  PubMed  Google Scholar 

  21. Wolin MS (2000) Interactions of oxidants with vascular signaling systems. Arterioscler Thromb Vasc Biol 20:1430–1442

    CAS  PubMed  Google Scholar 

  22. Carr AC, McCall MR, Frei B (2000) Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection. Arterioscler Thromb Vasc Biol 20:1716–1723

    CAS  PubMed  Google Scholar 

  23. Schultz D, Harrison DG (2000) Quest for fire: seeking the source of pathogenic oxygen radicals in atherosclerosis (editorial). Arterioscler Thromb Vasc Biol 20:1412–1413

    CAS  PubMed  Google Scholar 

  24. Flavahan NA (1993) Lysophosphatidylcholine modifies G protein-dependent signaling in porcine endothelial cells. Am J Physiol 264: H722–H727

    Google Scholar 

  25. Harrison DG (1997) Cellular and molecular mechanisms of endothelial cell dysfunction. J Clin Invest 100:2153–2157

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Wever RM, Lüscher TF, Cosentino F, Rabelink T (1998) Atherosclerosis and the two faces of endothelial nitric oxide synthase. Circulation 97:108–112

    CAS  PubMed  Google Scholar 

  27. Vergnani L, Hatrik S, Ricci F, Passaro A, Manzoli N, Zuliani G et al (2000) Effect of native and oxidized low-density lipoprotein on endothelial nitric oxide and superoxide production: key role of L-arginine availability. Circulation 101:1261–1266

    CAS  PubMed  Google Scholar 

  28. Cooke JP (2000) Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 20:2032–2037

    CAS  PubMed  Google Scholar 

  29. Boger RH, Sydow K, Borlak J, Thum T, Lenzen H, Schubert B et al (2000) LDL cholesterol up-regulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res 87: 99–105

    CAS  PubMed  Google Scholar 

  30. Minor RLJ, Myers PR, Guerra RJ, Bates JN, Harrison DG (1990) Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta. J Clin Invest 86:2109–2116

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Wilcox JN, Subramanian RR, Sundell CL, Tracey WR, Pollock JS, Harrison DG (1997) Expression of multiple isoforms of nitric oxide synthase in normal and atherosclerotic vessels. Arterioscler Thromb Vasc Biol 17:2479–2488

    CAS  PubMed  Google Scholar 

  32. Behr-Roussel D, Rupin A, Simonet S, Bonhomme E, Coumailleau S, Cordi A et al (2000) Effect of chronic treatment with the inducible nitric oxide synthase inhibitor N-iminoethyl-L-lysine or with L-arginine on progression of coronary and aortic atherosclerosis in hypercholesterolemic rabbits. Circulation 102:1033–1038

    CAS  PubMed  Google Scholar 

  33. Yogo K, Shimokawa H, Funakoshi H, Kandabashi T, Miyata K, Okamoto S et al (2000) Different vasculoprotective roles of NO synthase isoforms in vascular lesion formation in mice. Arterioscler Thromb Vasc Biol 20:E96–E100

    Google Scholar 

  34. Benigni A, Remuzzi G (1999) Endothelin antagonists. Lancet 353:133–138

    CAS  PubMed  Google Scholar 

  35. Pernow J, Wang QD (1997) Endothelin in myocardial ischemia and reperfusion. Cardiovasc Res 33:518–526

    CAS  PubMed  Google Scholar 

  36. Levin ER (1996) Endothelins. N Engl J Med 333:356–363

    Google Scholar 

  37. Yang Z, Richard D, Von Segesser L, Bauer E, Stulz P, Turina M et al (1990) Threshold concentrations of endothelin-1potentiate contractions to norepinephrine and serotonin in human arteries: a new mechanism of vasospasm? Circulation 82:188–195

    CAS  PubMed  Google Scholar 

  38. Lerman A, Holmes DR Jr, Bell MR, Garratt KN, Nishimura RA, Burnett JC (1995) Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans. Circulation 92:2426–2431

    CAS  PubMed  Google Scholar 

  39. Haynes WG, Webb DJ (1994) Contribution of endogenous generation of endothelin-i to basal vascular tone. Lancet 344:852–854

    CAS  PubMed  Google Scholar 

  40. Haynes WG, Strachan FE, Webb DJ (1995) Endothelin ETA and ETB receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation 92:357–363

    CAS  PubMed  Google Scholar 

  41. Dagassen PH, Breu V, Clozel M, Künzli A, Vogt P, Turina M et al (1996) Up-regulation of endothelin-B receptors in atherosclerotic human coronary arteries. J Cardiovasc Pharmacol 27:147–153

    Google Scholar 

  42. Kahler J, Köster R, Paul M, Hamm CW, Meinertz T (1997) Endo-theline bei kardiovaskulären Erkrankungen. Z Kardiol 86:406–416

    CAS  PubMed  Google Scholar 

  43. Lerman A, Edwards BS, Halle, JW, Heublein DM, Sandberg SM, Burnett JC (1991) Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis in humans. N Engl J Med 325:991–1001

    Google Scholar 

  44. Zeiher AM, Goebel H, Schächinger V, Ihling C (1995) Tissue endo-thelin-i immunoreactivity in the active coronary atherosclerotic plaque. A clue to the mechanism of increased vasoreactivity of the culprit lesion in unstable angina. Circulation 91:941–947

    CAS  PubMed  Google Scholar 

  45. Bogaty P, Hackett D, Davies G, Maseri A (1994) Vasoreactivity of the culprit lesion in unstable angina. Circulation 90:5–11

    CAS  PubMed  Google Scholar 

  46. Zeiher AM, Ihling C, Pistorius K, Schächinger V, Schäfer HE (1994) Increased tissue endothelin immunoreactivity in atherosclerotic lesions associated with acute coronary syndromes. Lancet 344: 1405–1406

    CAS  PubMed  Google Scholar 

  47. Bassenge E, Heusch G (1990) Endothelial and neuro-humoral control of coronary blood flow in health and disease. Rev Physiol Biochem Pharmacol 116:77–165

    CAS  PubMed  Google Scholar 

  48. Moncada S, Gryglewski R, Bunting S, Vane JR (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263:663–665

    CAS  PubMed  Google Scholar 

  49. Palmer RMJ, Ashton DS, Moncada S (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664–666

    CAS  PubMed  Google Scholar 

  50. Bhagat K, Collier J, Vallance P (1995) Vasodilation to arachidonic acid in humans. Circulation 92:2113–2118

    CAS  PubMed  Google Scholar 

  51. Vallance P, Collier J, Bhagat K (1997) Infection, inflammation, and infarction: does acute endothelial dysfunction provide a link. Lancet 349:1391–1392

    CAS  PubMed  Google Scholar 

  52. Cohen RA, Vanhoutte PM (1995) Endothelium-dependent hyper-polarization — beyond nitric oxide and cyclic GMP. Circulation 92:3337–3349

    CAS  PubMed  Google Scholar 

  53. Pagliaro P, Rastaldo R, Paolocci N, Gattullo D, Losano G (2000) The endothelium-derived hyperpolarizing factor: does it play a role in vivo and is it involved in the regulation of vascular tone only? Ital Heart J 1:264–268

    CAS  PubMed  Google Scholar 

  54. Popp R, Fleming I, Busse R. Pulsatile stretch in coronary arteries elicits release of endothelium- derived hyperpolarizing factor: a modulator of arterial compliance. Circ Res 1998 82:696–703

    CAS  PubMed  Google Scholar 

  55. Brandes RP, Schmitz-Winnenthal FH, Feletou M, Godecke A, Huang PL, Vanhoutte PM et al (2000) An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice. Proc Natl Acad Sc U S A 97:9747–9752

    CAS  Google Scholar 

  56. Honing ML, Smits P, Morrison PJ, Rabelink TJ (2000) Bradykinin-induced vasodilation of human forearm resistance vessels is primarily mediated by endothelium-dependent hyperpolarization. Hypertension 35:1314–1318

    CAS  PubMed  Google Scholar 

  57. Shimokawa H, Yasutake H, Fujii K, Owada MK, Nakaike R, Fuku-moto Y et al (1996) The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol 28:703–711

    CAS  PubMed  Google Scholar 

  58. Bauersachs J (1996) Nitric oxide attenuates the release of endothelium-derived hyperpolarizing factor. Circulation 94:3341–3347

    CAS  PubMed  Google Scholar 

  59. Nishikawa Y, Stepp DW, Chilian WM (2000) Nitric oxide exerts feedback inhibition on EDHF-induced coronary arteriolar dilation in vivo. Am J Physiol Heart Circ Physiol 279:H45-H465

    Google Scholar 

  60. Oskarsson HJ, Heistad DD (1997) Oxidative stress produced by angiotensin too. Implications for hypertension and vascular injury. Circulation 95:557–559

    CAS  PubMed  Google Scholar 

  61. Diet F, Pratt RE, Berry GJ, Momose N, Gibbons GH, Dzau VJ (1997) Increased accumulation of tissue ACE in human atherosclerotic coronary artery disease. Circulation 94:2756–2767

    Google Scholar 

  62. Schieffer B, Schieffer E, Hilfiker-Kleiner D, Hilfiker A, Kovanen PT, Kaartinen M et al (2000) Expression of angiotensin II and inter-leukin 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability. Circulation 101:1372–1378

    CAS  PubMed  Google Scholar 

  63. Zeiher AM (1996) Endothelial vasodilator dysfunction: pathogenetic link to myocardial ischemia or epiphenomenon. Lancet 348:S10–S12

    Google Scholar 

  64. Moroi M, Zhang L, Yasuda T, Virmani R, Gold HK, Fishman MC et al (1998) Interaction of genetic deficiency of endothelial nitric oxide, gender, and pregnancy in vascular response to injury in mice. J Clin Invest 101:1225–1232

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Barnes PJ, Karin M (1997) Nuclear factor-KB — a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336: 1066–1071

    CAS  PubMed  Google Scholar 

  66. Fichtischerer S, Rosenberger G, Walter DH, Breuer S, Dimmeier S, Zeiher AM (2000) Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 102:1000–1006

    Google Scholar 

  67. Fichtischerer S, Zeiher AM (2000) Endothelial dysfunction in acute coronary syndromes: association with elevated C-reactive protein levels. Ann Intern Med 32:515–518

    Google Scholar 

  68. Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy MA, Simson DC et al (1998) Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. 97:1695–1701

    CAS  Google Scholar 

  69. Libby P, Ridker PM (1999) Novel inflammatory markers of coronary risk. Theory versus practice. Circulation 100:1148–1150

    CAS  PubMed  Google Scholar 

  70. Pasceri V, Willerson JT, Yeh ET (2000) Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 102:2165–2168

    CAS  PubMed  Google Scholar 

  71. Lagrand WK, Visser CA, Hermens WT, Niessen HW, Verheugt FW, Wolbink GJ et al (1999) C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon? Circulation 100:96–102

    CAS  PubMed  Google Scholar 

  72. Torzewski M, Rist C, Mortensen RF, Zwaka TP, Bienek M, Walten-berger J et al (2000) C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis. Arterioscler Thromb Vasc Biol 20:2094–2099

    CAS  PubMed  Google Scholar 

  73. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH (1997) Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 336:973–979

    CAS  PubMed  Google Scholar 

  74. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH (1998) Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 98:731–733

    CAS  PubMed  Google Scholar 

  75. Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB (1997) Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 349:462–466

    CAS  PubMed  Google Scholar 

  76. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB et al (1994) The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 331:417–424

    CAS  PubMed  Google Scholar 

  77. Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L (2000) Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during instability in coronary artery disease (see comments). N Engl J Med 343:1139–1147

    CAS  PubMed  Google Scholar 

  78. Rader DJ (2000) Inflammatory markers of coronary risk. N Engl J Med 343:1179–1182

    CAS  PubMed  Google Scholar 

  79. Fichtischerer S, Rosenberger G, Zeiher AM (1999) Evidence for enhanced systemic oxidative stress in patients with acute coronary syndrome (abstract). Circulation 100:1756

    Google Scholar 

  80. Packard CJ, O’Reilly DS, Caslake MJ, McMahon AD, Ford I, Cooney J et al (2000) Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med 343:1148–1155

    CAS  PubMed  Google Scholar 

  81. Alexander RW (1998) Atherosclerosis as disease of redox-sensitive genes. Trans Am Clin Climatol Assoc 109:129–145

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Dimmeier S, Zeiher AM (1997) Nitric oxide and apoptosis: another paradigm for the double-edged role of nitric oxide. Nitric Oxide 1:275–281

    Google Scholar 

  83. Haunstetter A, Izumo S (1998) Apoptosis. Basic mechanisms and implications for cardiovascular disease. Circ Res 82:1111–1129

    CAS  PubMed  Google Scholar 

  84. Dimmeler S, Rippmann V, Weiland U, Haendeler J, Zeiher AM (1997) Angiotensin II induces apoptosis of human endothelial cells — protective effect of nitric oxide. Circ Res 81:75–83

    Google Scholar 

  85. Asai K, Kudej RK, Shen YT, Yang GP, Takagi G, Kudej AB et al (2000) Peripheral vascular endothelial dysfunction and apoptosis in old monkeys. Arterioscler Thromb Vasc Biol 20:1493–1499

    CAS  PubMed  Google Scholar 

  86. Dimmeler S, Haendeler J, Rippmann V, Nehls M, Zeiher AM (1996) Shear stress inhibits apoptosis of human endothelial cells. FEBS Lett 39971–74

    Google Scholar 

  87. Langille BL, O’Donnell F (1986) Reduction of arterial diameter produced by chronic decrease in blood flow are endothelium-dependent. Science 231:405–407

    CAS  PubMed  Google Scholar 

  88. Glagov S, Weisenberg E, Zarins CK, Stancunavicius T, Kolettis GJ (1987) Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 316:1371–1375

    CAS  PubMed  Google Scholar 

  89. Rudic RD, Shesely EG, Nobuyo M, Smithies O, Segal SS, Sessa WC (1998) Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. J Clin Invest 101:731–736

    CAS  PubMed Central  PubMed  Google Scholar 

  90. Niebauer J, Cooke JP (1996) Cardiovascular effects of exercise: role of endothelial shear stress. J Am Coll Cardiol 28:1652–1660

    CAS  PubMed  Google Scholar 

  91. Tronc F, Wassef M, Esposito B, Henrion D, Glagov S, Tedgui A (1996) Role of NO in flow-induced remodeling of the rabbit common carotid artery. Arterioscler Thromb Vasc Biol 16:1256–1262

    CAS  PubMed  Google Scholar 

  92. Pasterkamp G, Schoneveld AH, van der Wal AC, Haudenschild CC, Clarijs RJ, Becker AE et al (1998) Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox. J Am Coll Cardiol 32:655–662

    CAS  PubMed  Google Scholar 

  93. Schoenhagen P, Ziada KM, Kapadia SR, Crowe TD, Nissen SE, Tuzcu EM (2000) Extent and direction of arterial remodeling in stable versus unstable coronary syndromes: an intravascular ultrasound study. Circulation 101:598–603

    CAS  PubMed  Google Scholar 

  94. Falk E, Shah PK, Fuster V (1995) Coronary plaque disruption. Circulation 92:657–670

    CAS  PubMed  Google Scholar 

  95. Radomski MW, Moncada S (1993) Regulation of vascular homeostasis by nitric oxide. Thromb Haemost 70:36–41

    CAS  PubMed  Google Scholar 

  96. Zeiher AM, Schächinger V (1994) Coronary endothelial vasodilator dysfunction: clinical relevance and therapeutic implications. Z Kardiol 83 [Suppl 4] 7–14

    PubMed  Google Scholar 

  97. Quyyumi AA, Dakak N, Andrews NP, Gilligan DM, Panza JA, Cannon RO 3rd (1995) Contribution of nitric oxide to metabolic coronary vasodilation in the human heart. Circulation 92:320–326

    CAS  PubMed  Google Scholar 

  98. Quyyumi AA, Dakak N, Andrews NP, Husain S, Arora S, Gilligan DM et al (1995) Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis. J Clin Invest 95:1747–1755

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Zeiher AM, Drexler H, Wollschläger H, Saurbier B, Just H (1989) Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium. J Am Coll Cardiol 14:1181–1190

    CAS  PubMed  Google Scholar 

  100. Zeiher AM, Drexler H, Wollschläger H, Just H (1991) Endothelial dysfunction of the coronary microvasculature is associated with impaired coronary blood flow regulation in patients with early atherosclerosis. Circulation 84:1984–1992

    CAS  PubMed  Google Scholar 

  101. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW et al (1986) Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 315:1046–1051

    CAS  PubMed  Google Scholar 

  102. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    CAS  PubMed  Google Scholar 

  103. Nabel EG, Ganz P, Gordon JB, Alexander RW, Selwyn AP (1988) Dilation of normal and constriction of atherosclerotic coronary arteries caused by the cold pressor test. Circulation 77:43–52

    CAS  PubMed  Google Scholar 

  104. Cox DA, Vita JA, Treasure CB, Fish RD, Alexander RW, Ganz P et al (1989) Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans. Circulation 80:458–465

    CAS  PubMed  Google Scholar 

  105. Zeiher AM, Schächinger V, Minners J (1995) Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation 92:1094–1100

    CAS  PubMed  Google Scholar 

  106. Ravichandran LV, Johns RA, Rengasamy A (1995) Direct and reversible inhibition of endothelial nitric oxide synthase by nitric oxide. Am J Physiol 268:H2216–H2223

    Google Scholar 

  107. Newby DE (2000) Intracoronary infusions and the assessment of coronary blood flow in clinical studies. Heart 84:118–120

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Mallat Z, Benamer H, Hugel B, Benessiano J, Steg PG, Freyssinet JM et al (2000) Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 101:841–843

    CAS  PubMed  Google Scholar 

  109. Mutin M, Canavy I, Blann A, Bory M, Sampol J, Dignat-George F (1999) Direct evidence of endothelial injury in acute myocardial infarction and unstable angina by demonstration of circulating endothelial cells. Blood 93:2951–2958

    CAS  PubMed  Google Scholar 

  110. Zeiher AM, Drexler H, Wollschläger H, Just H (1991) Modulation of coronary vasomotor tone in humans: progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 83:391–401

    CAS  PubMed  Google Scholar 

  111. Treasure CB, Manoukian SV, Klein JL, Vita JA, Nabel EG, Renwick GH et al (1992) Epicardial coronary artery responses to acety-choline are impaired in hypertensive patients. Circ Res 71:776–1781

    CAS  PubMed  Google Scholar 

  112. Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish RD, Yeung AC et al (1990) Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation 81:491–497

    CAS  PubMed  Google Scholar 

  113. Egashira K, Inou T, Hirooka Y, Yamada A, Maruoka Y, Kai H et al (1993) Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions. J Clin Invest 91:29–37

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE (1994) Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol 24:1468–1474

    CAS  PubMed  Google Scholar 

  115. Harrison DG, Bates JN (1993) The nitrovasodilators. New ideas about old drugs. Circulation 87:1461–1467

    CAS  PubMed  Google Scholar 

  116. Marcus ML, Chilian WM, Kanatsuka H, Dellsperger KC, Eastham CL, Lamping KG (1990) Understanding the coronary circulation through studies at the microvascular level. Circulation 82:1–7

    CAS  PubMed  Google Scholar 

  117. Sellke FW, Armstrong ML, Harrison DG (1990) Endothelium-dependent vascular relaxation is abnormal in the coronary microcirculation of atherosclerotic primates. Circulation 81:1586–1593

    CAS  PubMed  Google Scholar 

  118. Dupouy P, Geschwind HJ, Pelle G, Gallot D, Larrazet F, el Ghalid A et al (1994) Evaluation of coronary vasomotricity by intracoronary ultrasonography. Arch Mal Coeur Vaiss 87:363–368

    CAS  PubMed  Google Scholar 

  119. Schächinger V, Britten M, Eisner M, Walter DH, Scharrer I, Zeiher AM (1999) A positive family history of premature coronary artery disease is associated with impaired endothelium-dependent coronary blood flow regulation. Circulation 100:1502–1508

    PubMed  Google Scholar 

  120. Casino PR, Kilcoyne CM, Quyyumi AA, Hoeg JM, Panza JA (1993) The role of nitric oxide in endothelium-dependent vasodilation of hypercholesterolemic patients. Circulation 88:2541–2547

    CAS  PubMed  Google Scholar 

  121. Casino PR, Kilcoyne CM, Quyyumi AA, Hoeg JM, Panza JA (1994) Investigation of decreased availability of nitric oxide precursor as the mechanism responsible for impaired endothelium-dependent vasodilation in hypercholesterolemic patients. J Am Coll Cardiol 23:844–850

    CAS  PubMed  Google Scholar 

  122. Quyyumi AA, Mulcahy D, Nadrews NP, Husain S, Panza JA, Cannon RO 3rd (1997) Coronary vascular nitric oxide activity in hypertension and hypercholesterolemia. Comparison of acetylcholine and substance P. Circulation 95:104–110

    CAS  PubMed  Google Scholar 

  123. Anderson TJ, Meredith IT, Charbonneau F, Yeung AC, Frei B, Selwyn AP et al (1996) Endothelium-dependent coronary vasomotion relates to the susceptibility of LDL to oxidation in humans. Circulation 93:1647–1650

    CAS  PubMed  Google Scholar 

  124. Zeiher AM, Drexler H, Saurbier B, Just H (1993) Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension. J Clin Invest 92:652–662

    CAS  PubMed Central  PubMed  Google Scholar 

  125. John S, Schmieder RE (2000) Impaired endothelial function in arterial hypertension and hypercholesterolemia: potential mechanisms and differences. J Hypertens 18:363–374

    CAS  PubMed  Google Scholar 

  126. Seiler C, Hess OM, Buechi M, Suter TM, Krayenbuehl HP (1993) Influence of serum cholesterol and other coronary risk factors on vasomotion of angiographically normal coronary arteries. Circulation 88:2139–2148

    CAS  PubMed  Google Scholar 

  127. Casino PR, Kilcoyne CM, Cannon RO 3rd, Quyyumi AA, Panza JA (1995) Impaired endothelium-dependent vascular relaxation in patients with hypercholesterolemia extends beyond the muscarinic receptor. Am J Cardiol 75:40–44

    CAS  PubMed  Google Scholar 

  128. Zeiher AM, Schächinger V, Hohnloser SH, Saurbier B, Just H (1994) Coronary atherosclerotic wall thickening and vascular reactivity in humans. Elevated high-density lipoprotein levels ameliorate abnormal vasoconstriction in early atherosclerosis. Circulation 89:2525–2532

    CAS  PubMed  Google Scholar 

  129. Skyrme-Jones RA, O’Brien RC, Luo M, Meredith IT (2000) Endothelial vasodilator function is related to low-density lipoprotein particle size and low-density lipoprotein vitamin E content in type 1 diabetes. J Am Coll Cardiol 35:292–299

    CAS  Google Scholar 

  130. Lupattelli G, Lombardini R, Schillaci G, Ciuffetti G, Marchesi S, Siepi D et al (2000) Flow-mediated vasoactivity and circulating adhesion molecules in hypertriglyceridemia: association with small, dense LDL cholesterol particles. Am Heart J 140:521–526

    CAS  PubMed  Google Scholar 

  131. McNeill KL, Fontana L, Russell-Jones DL, Rajman I, Ritter JM, Chowienczyk PJ (2000) Inhibitory effects of low-density lipoproteins from men with type II diabetes on endothelium-dependent relaxation. J Am Coll Cardiol 35:1622–1627

    CAS  PubMed  Google Scholar 

  132. Sattar N, Pétrie JR, Jaap AJ (1998) The atherogenic lipoprotein phenotype and vascular endothelial dysfunction. Atherosclerosis 138:229–235

    CAS  PubMed  Google Scholar 

  133. Brush JE, Faxon DP, Salmon S, Jacobs AK, Ryan TJ (1992) Abnormal endothelium-dependent coronary vasomotion in hypertensive patients. J Am Coll Cardiol 19:809–815

    PubMed  Google Scholar 

  134. Antony I, Aptecar E, Lerebours G, Nitenberg A (1994) Coronary artery constriction caused by cold pressor test in human hypertension. Hypertension 24:212–219

    CAS  PubMed  Google Scholar 

  135. Frielingsdorf J, Seiler C, Kaufmann P, Vassalli G, Suter T, Hess OM (1996) Normalization of abnormal vasomotion by calcium antagonists in patients with hypertension. Circulation 93:1380–1387

    CAS  PubMed  Google Scholar 

  136. Alexander RW (1995) Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension 25:155–161

    CAS  PubMed  Google Scholar 

  137. Huang PL, Huang ZH, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA et al (1995) Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377:239–242

    CAS  PubMed  Google Scholar 

  138. Forte P, Copland M, Milne E, Sutherland J, Benjamin N (1997) Basal nitric oxide synthesis in essential hypertension. Lancet 349:837–842

    CAS  PubMed  Google Scholar 

  139. Taddei S, Viridis A, Mattei P, Arzilli F, Salvetti A (1992) Endothe-lium-derived forearm vasodilation is reduced in normotensive subjects with family history of hypertension. J Cardiovasc Pharmacol 20:S193–S195

    Google Scholar 

  140. Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA (1994) Impaired endothelium-dependent vasodilation in patients with essential hypertension: evidence that the abnormality is not at the muscarinic receptor level. J Am Coll Cardiol 23:1610–1616

    CAS  PubMed  Google Scholar 

  141. Taddei S, Virdis A, Mattei P, Ghiadoni L, Gennari A, Fasolo CB et al (1995) Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation 91:1981–1987

    CAS  PubMed  Google Scholar 

  142. Linder L, Kiowski W, Buhler FR, Lüscher TF (1990) Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo: blunted response in essential hypertension. Circulation 81:1762–1767

    CAS  PubMed  Google Scholar 

  143. Panza JA, Garcia CE, Kilcoyne CM, Quyyumi AA, Cannon RO 3rd (1995) Impaired endothelium-dependent vasodilation in patients with essential hypertension: evidence that nitric oxide abnormality is not localized to a single signal transduction pathway. Circulation 91:1732–1738

    CAS  PubMed  Google Scholar 

  144. Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA (1993) Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 87:1468–1474

    CAS  PubMed  Google Scholar 

  145. Cockcroft JR, Chowienczyk PJ, Benjamin N, Ritter JM (1994) Preserved endothelium-dependent vasodilation in patients with essential hypertension. N Engl J Med 330:1036–1040

    CAS  PubMed  Google Scholar 

  146. Laurent S, Lacolley P, Brunei P, Laloux B, Pannier B, Safar M (1990) Flow-dependent vasodilation of brachial artery in essential hypertension. Am J Physiol 258:H1004–H1111

    Google Scholar 

  147. Lüscher TF (1994) The endothelium and cardiovascular disease — a complex relation. N Engl J Med 330:1081–1083

    PubMed  Google Scholar 

  148. Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinson J et al (1993) Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 88:2149–2155

    CAS  PubMed  Google Scholar 

  149. Woo KS, Chook P, Leong HC, Huang XS, Celermajer DS (2000) The impact of heavy passive smoking on arterial endothelial function in modernized Chinese. J Am Coll Cardiol 36:1228–1232

    CAS  PubMed  Google Scholar 

  150. Enderle MD, Pfohl M, Kellermann N, Haering HU, Hoffmeister HM (2000) Endothelial function, variables of fibrinolysis and coagulation in smokers and healthy controls. Haemostasis 30:149–158

    CAS  PubMed  Google Scholar 

  151. Raitakari OT, Adams MR, McCredie RJ, Griffiths KA, Celermajer DS (1999) Arterial endothelial dysfunction related to passive smoking is potentially reversible in healthy young adults. Ann Intern Med 130:578–581

    CAS  PubMed  Google Scholar 

  152. Heitzer T, Just H, Münzel T (1996) Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation 94:6–9

    CAS  PubMed  Google Scholar 

  153. Kugiyama K, Yasue H, Ohgushi M, Motoyama T, Kawano H, Inobe Y et al (1996) Deficiency in nitric oxide bioactivity in epicardial coronary arteries of chronic smokers. J Am Coll Cardiol 28:1161–1167

    CAS  PubMed  Google Scholar 

  154. Schächinger V, Halle M, Minners J, Berg A, Zeiher AM (1997) Lipoprotein (a) selectively impairs receptor-mediated endothelial vasodilator function of the human coronary circulation. J Am Coll Cardiol 30:927–934

    PubMed  Google Scholar 

  155. Morrow JD, Frei B, Longmire AW, Gaziano M, Lynch SM, Shyr Y et al (1995) Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a cause of oxidative damage. N Engl J Med 332:1198–1203

    CAS  PubMed  Google Scholar 

  156. Reilly M, Delanty N, Lawson JA, FitzGerald GA (1996) Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation 94:19–25

    CAS  PubMed  Google Scholar 

  157. Hoffman D, Hecht SS, Ornaf RM, Wynder EL, Tso TC (1976) Chemical studies on tobacco smoke. XLII. Nitrosonornicotine: presence in tobacco, formation and carcinogenicity. IARC Sci Publ 14:307–320

    Google Scholar 

  158. Bokhoven C, Kodama M (1961) Amounts of oxides of nitrogen and carbon monoxide in cigarette smoke, with and without inhalation. Nature 192:458–459

    CAS  PubMed  Google Scholar 

  159. Heitzer T, Yla-Herttuala S, Luoma J, Kurz S, Munzel T, Just H et al (1996) Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia. Role of oxidized LDL. Circulation 93:1346–1353

    CAS  PubMed  Google Scholar 

  160. Newby DE, Wright RA, Labinjoh C, Ludlam CA, Fox KA, Boon NA et al (1999) Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking: a mechanism for arterial thrombosis and myocardial infarction. Circulation 99:1411–1415

    CAS  PubMed  Google Scholar 

  161. Kaufmann PA, Gnecchi-Ruscone T, di Terlizzi M, Schafers KP, Luscher TF, Camici PG (2000) Coronary heart disease in smokers: vitamin C restores coronary microcirculatory function. Circulation 102:1233–1238

    CAS  PubMed  Google Scholar 

  162. Heitzer T, Yla HS, Wild E, Luoma J, Drexler H (1999) Effect of vitamin E on endothelial vasodilator function in patients with hypercholesterolemia, chronic smoking or both. J Am Coll Cardiol 33: 499–505

    CAS  PubMed  Google Scholar 

  163. Raitakari OT, Adams MR, McCredie RJ, Griffiths KA, Stocker R, Celermajer DS (2000) Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect. J Am Coll Cardiol 35:1616–1621

    CAS  PubMed  Google Scholar 

  164. Heitzer T, Brockhoff C, Mayer B, Warnholtz A, Mollnau H, Henne S et al (2000) Tetrahydrobiopterin improves endothelium-dependent vasodilation in chronic smokers: evidence for a dysfunctional nitric oxide synthase. Circ Res 86:E36–E41

    Google Scholar 

  165. Campisi R, Czernin J, Schoder H, Sayre JW, Schelbert HR (1999) L-Arginine normalizes coronary vasomotion in long-term smokers. Circulation 99:491–497

    CAS  PubMed  Google Scholar 

  166. Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA (1993) Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 88: 2510–2516

    CAS  PubMed  Google Scholar 

  167. Lambert J, Aarsen M, Donker AJM, Stehouwer CDA (1996) Endothelium-dependent and -independent vasodilation of large arteries in normoalbuminuric insulin-dependent diabetes mellitus. Arte-rioscler Thromb Vasc Biol 16:705–711

    CAS  Google Scholar 

  168. Makimattila S, Virkamaki A, Groop PH, Cockcroft J, Utriainen T, Fagerudd J et al (1996) Chronic hyperglycemia impairs endothelial function and insulin sensitivity via different mechanisms in insulin-dependent diabetes mellitus. Circulation 94:1276–1282

    CAS  PubMed  Google Scholar 

  169. Poston L, Taylor PD (1995) Endothelium-mediated vascular function in insulin-dependent diabetes mellitus. Clin Sci 88:245–255

    CAS  PubMed  Google Scholar 

  170. Poredos P, Kek A (2000) Relation of blunted dilation of the brachial artery in insulin-dependent diabetes mellitus to microalbuminuria. Am J Cardiol 86:364–367

    CAS  PubMed  Google Scholar 

  171. Pieper GM (1998) Review of alterations in endothelial nitric oxide production in diabetes — protective role of arginine on endothelial dysfunction. Hypertension 31:1047–1060

    CAS  PubMed  Google Scholar 

  172. Cardillo C, Nambi SS, Kilcoyne CM, Choucair WK, Katz A, Quon MJ et al (1999) Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation 100:820–825

    CAS  PubMed  Google Scholar 

  173. Cardillo C, Kilcoyne CM, Nambi SS, Cannon RO, III, Quon MJ, Panza JA (1998) Vasodilator response to systemic but not to local hyperinsulinemia in the human forearm. Hypertension 32:740–745

    CAS  PubMed  Google Scholar 

  174. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD (1994) Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 94:1172–1179

    CAS  PubMed Central  PubMed  Google Scholar 

  175. Mullen MJ, Wright D, Donald AE, Thorne S, Thomson H, Deanfield JE (2000) Atorvastatin but not L-arginine improves endothelial function in type I diabetes mellitus: a double-blind study. J Am Coll Cardiol 36:410–416

    CAS  PubMed  Google Scholar 

  176. Evans M, Anderson RA, Graham J, Ellis GR, Morris K, Davies S et al (2000) Ciprofibrate therapy improves endothelial function and reduced postprandial lipemia and oxidative stress in type 2 diabetes mellitus. Circulation 101:1773–1779

    CAS  PubMed  Google Scholar 

  177. Skyrme-Jones RA, O’Brien RC, Berry KL, Meredith IT (2000) Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study. J Am Coll Cardiol 36:94–102

    CAS  PubMed  Google Scholar 

  178. Ting HH, Timimi FK, Boles KS, Creager SJ, Ganz P, Creager MA (1996) Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 97:22–28

    CAS  PubMed Central  PubMed  Google Scholar 

  179. Celermajer DS, Sorensen KE, Spiegelhalter DS, Georgakopoulos D, Robinson J, Deanfield JE (1994) Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol 24:471–476

    CAS  PubMed  Google Scholar 

  180. Vasa M, Breitschopf K, Zeiher AM, Dimmeier S (2000) Nitric oxide activates telomerase and delays endothelial cell senescence. Circ Res 87:540–542

    CAS  PubMed  Google Scholar 

  181. Clarkson P, Celermajer DS, Powe AJ, Donald AE, Henry RM, Deanfield JE (1997) Endothelium-dependent dilation is impaired in young healthy subjects with a family history of premature coronary disease. Circulation 96:3378–3383

    CAS  PubMed  Google Scholar 

  182. Dahlén GH (1995) Lp(a) lipoprotein in cardiovascular disease. Atherosclerosis 108:111–126

    Google Scholar 

  183. Armstrong VW, Cremer P, Eberle E, Manke A, Schulze F, Wieland H et al (1986) The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis: dependence on serum LDL levels. Atherosclerosis 62:249–257

    CAS  PubMed  Google Scholar 

  184. Cremer P, Nagel D, Labrot B, Mann H, Muche R, Elster H et al (1994) Lipoprotein Lp(a) as a predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Göttingen Risk Incidence and Prevalence Study (GRIPS). Europ J Clin Invest 24:444–453

    CAS  PubMed  Google Scholar 

  185. Tsurumi Y, Nagashima H, Ichikawa KI, Sumiyoshi T, Hosoda S (1995) Influence of plasma lipoprotein(a) levels on coronary vasomotor response to acetylcholine. J Am Coll Cardiol 26:1242–1250

    CAS  PubMed  Google Scholar 

  186. Utermann G (1989) The mysteries of lipoprotein (a). Science 246: 904–910

    CAS  PubMed  Google Scholar 

  187. Grainger DJ, Kemp PR, Metcalfe JC, Liu AC, Lawn RM, Williams NR et al (1995) The serum concentration of active transforming growth factor-b is severely depressed in advanced atherosclerosis. Nature Med 1:74–79

    CAS  PubMed  Google Scholar 

  188. Inoue N, Venema RC, Sayegh HS, Ohara Y, Murphy TJ, Harrison DG (1995) Molecular regulation of the bovine endothelial cell nitric oxide synthase by transforming growth factor-bj. Arterioscler Thromb Vasc Biol 15:1255–1261

    CAS  PubMed  Google Scholar 

  189. Hajjar KA, Gavish D, Breslow JL, Nachman RL (1989) Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature 339:303–305

    CAS  PubMed  Google Scholar 

  190. Rath M, Niendorf A, Reblin T, Dietel M, Krebber HJ, Beisiegel U (1989) Detection and quantitation of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis 9:579–592

    CAS  PubMed  Google Scholar 

  191. Lawn RM, Wade DP, Hammer RE, Chiesa G, Verstuyft JG, Rubin EM (1992) Atherogenesis in transgenic mice expressing human apolipoprotein (a). Nature 360:670–672

    CAS  PubMed  Google Scholar 

  192. Nielsen LB, Nordestgaard BG, Stender S, Niendorf A, Kjeldsen K (1995) Transfer of lipoprotein (a) and LDL into aortic intima in normal and in cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol 15:1492–1502

    CAS  PubMed  Google Scholar 

  193. Scanu A, Fless GM (1990) Lipoprotein (a): heterogeneity and biological relevance. J Clin Invest 85:1709–1715

    CAS  PubMed Central  PubMed  Google Scholar 

  194. Haberland ME, Fless GM, Scanu AM, Fogelman AM (1992) Malon-dialdehyde modification of lipoprotein(a) produces avid uptake by human monocyte-macrophages. J Biol Chem 267:4143–4151

    CAS  PubMed  Google Scholar 

  195. Zioncheck TF, Powell LM, Rice GC, Eaton DL, Lawn RM (1991) Interaction of recombinant apolipoprotein (a) and Lp(a) with macrophages. J Clin Invest 87:767–771

    CAS  PubMed Central  PubMed  Google Scholar 

  196. Galle J, Bengen J, Schollmeyer P, Wanner C (1995) Impairment of endothelium-dependent dilation in rabbit arteries by oxidized lipoprotein (a). Role of oxygen-derived radicals. Circulation 92: 1582–1589

    CAS  PubMed  Google Scholar 

  197. Bellamy MF, McDowell IFW, Ramsey MW, Brownlee M, Bones C, Newcombe RG et al (1998) Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults. Circulation 98:1848–1852

    CAS  PubMed  Google Scholar 

  198. Woo KS, Chook P, Lolin YI, Cheung ASP, Chan LT, Sun YY et al (1997) Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. Circulation 96:2542–2544

    CAS  PubMed  Google Scholar 

  199. Malinow MR (1995) Plasma homocyst(e)ine and arterial occlusive disease: a mini review. Clin Chem 41:173–176

    CAS  PubMed  Google Scholar 

  200. Verhoef P, Stampfer MJ (1995) Prospective studies of homocysteine and cardiovascular disease. Nutr Rev 53:283–288

    CAS  PubMed  Google Scholar 

  201. Upchurch GR Jr, Welch GN, Fabian AJ, Freedman JE, Johnson JL, Keaney JFJ et al (1997) Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving gluthatione peroxidase. J Biol Chem 272:17012–17017

    CAS  PubMed  Google Scholar 

  202. Tawakol A, Omland T, Gerhard M, Wu JT, Creager MA (1997) Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation 95:1119–1121

    CAS  PubMed  Google Scholar 

  203. Chambers JC, McGregor A, Jean-Marie J, Obeid OA, Kooner JS (1999) Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 99:1156–1160

    CAS  PubMed  Google Scholar 

  204. Woo KS, Chook P, Lolin YI, Sanderson JE, Metreweli C, Celermajer DS (1999) Folic acid improves arterial endothelial function in adults with hyperhomocysteinemia. J Am Coll Cardiol 34:2002–2006

    CAS  PubMed  Google Scholar 

  205. Chambers JC, Ueland PM, Obeid OA, Wrigley J, Refsum H, Kooner JS (2000) Improved vascular endothelial function after oral B vitamins: an effect mediated through reduced concentrations of free plasma homocysteine. Circulation 102:2479–2483

    CAS  PubMed  Google Scholar 

  206. Lentz SR, Erger RA, Dayal S, Maeda N, Malinow MR, Heistad DD et al (2000) Folate dependence of hyperhomocysteinemia and vascular dysfunction in cystathionine beta-synthase-deficient mice. Am J Physiol Heart Circ Physiol 279:H970–H975

    Google Scholar 

  207. Title LM, Cummings PM, Giddens K, Genest JJ Jr, Nassar BA (2000) Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 36:758–765

    CAS  PubMed  Google Scholar 

  208. Wilmink HW, Stroes ES, Erkelens WD, Gerritsen WB, Wever R, Banga JD et al (2000) Influence of folic acid on postprandial endothelial dysfunction. Arterioscler Thromb Vasc Biol 20:185–188

    CAS  PubMed  Google Scholar 

  209. Yoon Y, Song J, Hong SH, Kim JQ (2000) Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease. Clin Chem 46:1626–1630

    CAS  PubMed  Google Scholar 

  210. Philip I, Plantefeve G, Vuillaumier-Barrot S, Vicaut E, LeMarie C, Henrion D et al (1999) G894T polymorphism in the endothelial nitric oxide synthase gene is associated with an enhanced vascular responsiveness to phenylephrine. Circulation 99:3096–3098

    CAS  PubMed  Google Scholar 

  211. Guzik TJ, West NE, Black E, McDonald D, Ratnatunga C, Pillai R et al (2000) Functional effect of the C242T polymorphism in the NAD(P)H oxidase p22 phox gene on vascular superoxide production in atherosclerosis. Circulation 102:1744–1747

    CAS  PubMed  Google Scholar 

  212. Inoue N, Kawashima S, Kanazawe K, Yamada S, Akita H, Yokoyama M (1998) Polymorphism of the NADH/NADPH oxidase p22 phox gene in patients with coronary artery disease. Circulation 97:135–137

    CAS  PubMed  Google Scholar 

  213. Schächinger V, Britten M, Dimmeler S, Zeiher AM (2001) NADH/ NADPH oxidase p22 phox gene polymorphism is associated with improved coronary endothelial vasodilator function. Eur Heart J 22:94–99

    Google Scholar 

  214. Celermajer DS, Sorensen KE, Barley J, Jeffrey J, Carter N, Deanfield JE (1994) Angiotensin-Converting enzyme genotype is not associated with endothelial dysfunction in subjects without other coronary risk factors. Atherosclerosis 111:121–126

    CAS  PubMed  Google Scholar 

  215. Prasad A, Narayanan S, Waclawiw MA, Epstein N, Quyyumi AA(2000) The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity. J Am Coll Cardiol 36:1579–1586

    CAS  PubMed  Google Scholar 

  216. Perticone F, Cerevolo R, Maio R, Ventura G, Zingone A, Perrotti N et al (1998) Angiotensin-Converting enzyme gene polymorphism is associated with endothelium-dependent vasodilation in never treated hypertensive patients. Hypertension 31:900–905

    CAS  PubMed  Google Scholar 

  217. Rosenthal N, Schwartz RS (1998) In search of perverse polymorphisms (editorial) (see comments). N Engl J Med 338:122–124

    CAS  PubMed  Google Scholar 

  218. Walter DH, Zeiher AM (2000) Genetic risk factors for myocardial infarct. Herz 25:7–14

    CAS  PubMed  Google Scholar 

  219. Lüscher TF, Richard V, Yang Z (1990) Interaction between endo-thelium-derived nitric oxide and SIN-1 in human and porcine blood vessels. J Cardiovasc Pharmacol 14:76–80

    Google Scholar 

  220. Schächinger V, Zeiher AM (1995) Quantitative assessment of coronary vasoreactivity in humans in vivo: importance of baseline vasomotor tone in atherosclerosis. Circulation 2087–2094

    Google Scholar 

  221. Adams MR, Robinson J, McCredie R, Seale JP, Sorensen KE, Deanfield JE et al (1998) Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis. J Am Coll Cardiol 32:123–127

    CAS  PubMed  Google Scholar 

  222. Diaz MN, Frei B, Vita JA, Keaney JFJ (1997) Antioxidants and atherosclerotic heart disease. N Engl J Med 337:408–416

    CAS  PubMed  Google Scholar 

  223. Münzel T, Sayegh H, Freeman BA, Tarpey MM, Harrison DG (1995) Evidence for enhanced vascular superoxide anion production in nitrate tolerance. J Clin Invest 95:187–194

    PubMed Central  PubMed  Google Scholar 

  224. Brandes RP, Kim D, Schmitz-Winnenthal FH, Amidi M, Godecke A, Mulsch A et al (2000) Increased nitrovasodilator sensitivity in endothelial nitric oxide synthase knockout mice: role of soluble guanylyl cyclase. Hypertension 35:231–236

    CAS  PubMed  Google Scholar 

  225. Bauersachs J, Bouloumie A, Mulsch A, Wiemer G, Fleming I, Busse R (1998) Vasodilator dysfunction in aged spontaneously hypertensive rats: changes in NO synthase III and soluble guanylyl cyclase expression, and in superoxide anion production. Cardiovasc Res 37:772–779

    CAS  PubMed  Google Scholar 

  226. Mulsch A, Bauersachs J, Schafer A, Stasch JP, Kast R, Busse R (1997) Effect of YC-1, an NO-independent, superoxide-sensitive stimulator of soluble guanylyl cyclase, on smooth muscle responsiveness to nitrovasodilators. Br J Pharmacol 120:681–689

    CAS  PubMed Central  PubMed  Google Scholar 

  227. Ruetten H, Zabel U, Linz W, Schmidt HH (1999) Downregulation of soluble guanylyl cyclase in young and aging spontaneously hypertensive rats. Circ Res 85:534–541

    CAS  PubMed  Google Scholar 

  228. MacAlpin R (1980) Contribution of dynamic vascular wall thickening to luminal narrowing during coronary arterial constriction. Circulation 60:296–301

    Google Scholar 

  229. Maseri A, Chierchia S, Kaski J (1985) Mixed angina pectoris. Am J Cardiol 56:31E-32E

    Google Scholar 

  230. Zeiher AM, Krause T, Schächinger V, Minners J, Moser E (1995) Impaired endothelium-dependent vasodilation of coronary resistance vessels is associated with exercise-induced myocardial ischemia. Circulation 91:2345–2352

    CAS  PubMed  Google Scholar 

  231. Meredith IT, Yeung AC, Weidinger FF, Anderson TJ, Uehata A, Ryan TJ et al (1993) Role of impaired endothelium-dependent vasodilation in ischemic manifestations of coronary artery disease. Circulation 87:V56–V66

    Google Scholar 

  232. Yeung AC, Vekshtein VI, Krantz DS, Vita JA, Ryan TJ, Ganz P et al (1991) The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med 325:1551–1556

    CAS  PubMed  Google Scholar 

  233. Stone PH, Krantz DS, McMahon RP, Goldberg AD, Becker LC, Chaitman BR et al (1999) Relationship among mental stress-induced ischemia and ischemia during daily life and during exercise: the psychophysiologic investigation of myocardial ischemia (PIMI) Study. J Am Coll Cardiol 33:1476–1484

    CAS  PubMed  Google Scholar 

  234. Britten MB, Klingenheben T, Walter DH, Eisner M, Zeiher AM, Schächinger V (1999) Mechanismus der Endotheldysfunktions-induzierten Myokardischämie (abstract). Z Kardiol 88 [Suppl 1]: 238

    Google Scholar 

  235. Andrews TC, Raby K, Barry J, Naimi BA, Allred E, Ganz P et al (1997) Effect of cholesterol reduction on myocardial ischemia in patients with coronary disease. Circulation 95:324–328

    CAS  PubMed  Google Scholar 

  236. Topol EJ, Yadav JS (2000) Recognition of the importance of embolization in atherosclerotic vascular disease. Circulation 101: 570–580

    CAS  PubMed  Google Scholar 

  237. Erbel R, Heusch G (2000) Coronary microembolization. J Am Coll Cardiol 36:22–24

    CAS  PubMed  Google Scholar 

  238. Zeiher AM, Schächinger V, Weitzel SH, Wollschläger H, Just H (1991) Intracoronary thrombus formation causes focal vasoconstriction of epicardial arteries in patients with coronary artery disease. Circulation 83:1519–1525

    CAS  PubMed  Google Scholar 

  239. Schächinger V, Britten MB, Zeiher AM (2000) Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 1899–1906

    Google Scholar 

  240. Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A (2000) Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 101: 948–954

    CAS  PubMed  Google Scholar 

  241. Halcox JP, Sharma A, Zalos G, Schenke WH, Nour KA, Panza JA, Quyyumi AA (2000) Coronary vasodilation and improvement in endothelial dysfunction with endothelin ET-A receptor blockade (abstract). Presented at the Scientific Sessions 2000 of the American Heart Association, New Orleans

    Google Scholar 

  242. Neunteufl T, Heher S, Katzenschlager R, Wolfl G, Kostner K, Maurer G et al (2000) Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol 86:207–210

    CAS  PubMed  Google Scholar 

  243. Schächinger V (1998) Therapeutic options to improve myocardial perfusion in coronary atherosclerosis (in German) Herz 23:116–129

    PubMed  Google Scholar 

  244. Levine GN, Keaney JF Jr, Vita JA (1995) Cholesterol reduction in cardiovascular disease. Clinical benefits and possible mechanisms. N Engl J Med 332:512–521

    CAS  PubMed  Google Scholar 

  245. Cannon RO III (2000) Cardiovascular benefit of cholesterol-lowering therapy: does improved endothelial vasodilator function matter? (editorial). Circulation 102:820–822

    PubMed  Google Scholar 

  246. Kuo L, Davis MJ, Cannon MS, Chilian WM (1992) Pathophysiological consequences of atherosclerosis extend into the coronary microcirculation. Restoration of endothelium-dependent responses by L-arginine. Circ Res 70:465–476

    CAS  PubMed  Google Scholar 

  247. Egashira K, Hirooka Y, Kuga T, Mohri M, Takeshita A (1996) Effects of L-arginine supplementation on endothelium-dependent coronary vasodilation in patients with angina pectoris and normal coronary angiograms. Circulation 94:130–134

    CAS  PubMed  Google Scholar 

  248. Quyyumi AA, Dakak N, Diodati JG, Gilligan DM, Panza JA, Cannon RO III (1997) Effect of L-arginine on human coronary endothelium-dependent and physiologic vasodilation. J Am Coll Cardiol 30: 1220–1227

    CAS  PubMed  Google Scholar 

  249. Lerman A, Burnett JC Jr, Higano ST, McKinley LJ, Holmes DR Jr (1998) Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 97:2123–2128

    CAS  PubMed  Google Scholar 

  250. Cooke JP, Singer AH, Tsao P, Zera P, Rowan RA, Billingham ME (1992) Antiatherogenic effects of L-arginine in the hypercholes-terolemic rabbit. J Clin Invest 90:1168–1172

    CAS  PubMed Central  PubMed  Google Scholar 

  251. Blum A, Hathaway L, Mincemoyer R, Schenke WH, Kirby M, Csako G et al (2000) Effects of oral L-arginine on endothelium-dependent vasodilation and markers of inflammation in healthy postmenopausal women. J Am Coll Cardiol 35:271–276

    CAS  PubMed  Google Scholar 

  252. Ohara Y, Peterson TE, Sayegh HS, Subramanian RR, Wilcox JN, Harrison DG (1995) Dietary correction of hypercholesterolemia in the rabbit normalizes endothelial superoxide anion production. Circulation 92:898–903

    CAS  PubMed  Google Scholar 

  253. Treasure CB, Klein JL, Weintraub WS, Talley JD, Stillabower ME, Kosinski AS et al (1995) Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med 332:481–487

    CAS  PubMed  Google Scholar 

  254. Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P (1995) The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med 332:488–493

    CAS  PubMed  Google Scholar 

  255. Egashira K, Takeshita A (1995) Beneficial effect of cholesterol-lowering therapy on endothelium-dependent coronary vasodilation in patients with hypercholesterolemia. Ann N Y Acad Sci 748: 622–625

    CAS  PubMed  Google Scholar 

  256. Vita JA, Yeung AC, Winniford M, Hodgson JM, Treasure CB, Klein JL et al (2000) Effect of cholesterol-lowering therapy on coronary endothelial vasomotor function in patients with coronary artery disease. Circulation 102:846–851

    CAS  PubMed  Google Scholar 

  257. Tamai O, Matsuoka H, Nishida H, Itabe H, Wada Y, Kohno K et al (1997) Single LDL-apheresis improves endothelium-dependent vasodilation in hypercholesterolemic humans. Circulation 95:76–82

    CAS  PubMed  Google Scholar 

  258. Goodfellow J, Bellamy MF, Ramsey MW, Jones CJ, Lewis MJ (2000) Dietary supplementation with marine omega-3-fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J Am Coll Cardiol 35:265–270

    CAS  PubMed  Google Scholar 

  259. Goode GK, Garcia S, Heagerty AM (1997) Dietary supplementation with marine fish oil improves in vitro small artery endothelial function in hypercholesterolemic patients: a double-blind placebo-controlled study. Circulation 96:2802–2807

    CAS  PubMed  Google Scholar 

  260. Gould KL, Martucci JP, Goldberg DI, Hess MJ, Edens RP, Latifi R et al (1994) Short-term cholesterol lowering decreases size and severity of perfusion abnormalities by positron emission tomography after dipyridamole in patients with coronary artery disease. A potential noninvasive marker of healing endothelium. Circulation 89:1530–1538

    CAS  PubMed  Google Scholar 

  261. Huggins GS, Pasternak RC, Alpert NM, Fischman AJ, Gewirtz H (1998) Effects of short-term treatment of hyperlipidemia on coronary vasodilator function and myocardial perfusion in regions having substantial impairment of baseline dilator reverse. Circulation 98:1291–1296

    CAS  PubMed  Google Scholar 

  262. Yokoyama I, Momomura S, Ohtake T, Yonekura K, Yang W, Koba-yakawa N et al (1999) Improvement of impaired myocardial vasodilatation due to diffuse coronary atherosclerosis in hyperchole-sterolemics after lipid-lowering therapy. Circulation 100:117–122

    CAS  PubMed  Google Scholar 

  263. Mostaza JM, Gomez MV, Gallardo F, Salazar ML, Martin-Jadraque R, Plaza-Celemin L et al (2000) Cholesterol reduction improves myocardial perfusion abnormalities in patients with coronary artery disease and average cholesterol levels. J Am Coll Cardiol 35:76–82

    CAS  PubMed  Google Scholar 

  264. Benzuly KH, Padgett RC, Kaul S, Piegors DJ, Armstrong ML, Heistad DD (1994) Functional improvement precedes structural regression of atherosclerosis. Circulation 89:1810–1818

    CAS  PubMed  Google Scholar 

  265. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, Macfarlane PW et al (1995) Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 333:1301–1307

    CAS  PubMed  Google Scholar 

  266. Scandinavian Simvastatin Survival Study Group (1994) Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383–1389

    Google Scholar 

  267. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG et al (1996) The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial Investigators. N Engl J Med 335:1001–1009

    CAS  PubMed  Google Scholar 

  268. Sacks FM, Ridker PM (1999) Lipid lowering and beyond: results from the CARE study on lipoproteins and inflammation. Cholesterol and Recurrent Events. Herz 24:51–56

    CAS  PubMed  Google Scholar 

  269. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman B, Leslie S, Stern T, for the MIRACL Investigators (2000) The myocardial ischemia reduction with aggressive cholesterol lowering (MIRACL) trial: effect of intensive atorvas-tatin treatment on early recurrent events after an acute coronary syndrome (abstract). Circulation 102:2672F

    Google Scholar 

  270. Schächinger V, Zeiher AM (1996) Alterations of coronary blood flow and myocardial perfusion in hypercholesterolemia. Heart 76: 295–298

    PubMed Central  PubMed  Google Scholar 

  271. Laufs U, La Fata V, Plutzky J, Liao JK (1998) Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 97:1129–1135

    CAS  PubMed  Google Scholar 

  272. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E (1999) Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 100:230–235

    CAS  PubMed  Google Scholar 

  273. Rosenson RS, Tangney CC (1998) Antiatherothrombotic properties of statins. Implications for cardiovascular event reduction. JAMA 279:1643–1650

    CAS  PubMed  Google Scholar 

  274. O’Driscoll G, Green D, Taylor RR (1997) Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within one month. Circulation 95:1126–1131

    PubMed  Google Scholar 

  275. Hornig B, Köhler C, Drexler H (1997) Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors in humans. Circulation 95:1115–1118

    CAS  PubMed  Google Scholar 

  276. Laurensen JB, Harrison DG (1997) Modulation of myocardial oxygen consumption through ACE inhibitors. NO effect? Circulation 95:14–16

    Google Scholar 

  277. Schneider CA, Voth E, Moka D, Baer FM, Melin J, Bol A et al (1999) Improvement of myocardial blood flow to ischemic regions by angiotensin-converting enzyme inhibition with quinaprilat IV: a study using (150) water dobutamine stress positron emission tomography. J Am Coll Cardiol 34:1005–1011

    CAS  PubMed  Google Scholar 

  278. Zhang X, Xie YW, Nasjletti A, Xu X, Wolin MS, Hintze TH (1997) ACE inhibitors promote nitric oxide accumulation to modulate myocardial oxygen consumption (see comments). Circulation 95:176–182

    PubMed  Google Scholar 

  279. Vaughan DE, Rouleau JL, Ridker PM, Arnold JM, Menapace FJ, Pfeffer MA (1997) Effects of ramipril on plasma fibrinolytic balance in patients with acute anterior myocardial infarction. HEART Study Investigators. Circulation 96:442–447

    CAS  PubMed  Google Scholar 

  280. Napoleone E, Di Santo A, Camera M, Tremoli E, Lorenzet R (2000) Angiotensin-converting enzyme inhibitors downregulate tissue factor synthesis in monocytes. Circ Res 86:139–143

    CAS  PubMed  Google Scholar 

  281. Soejima H, Ogawa H, Yasue H, Kaikita K, Takazoe K, Nishiyama K et al (1999) Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction. J Am Coll Cardiol 34:983–988

    CAS  PubMed  Google Scholar 

  282. Hernandez-Presa M, Bustos C, Ortego M, Tunon J, Renedo G, Ruiz-Ortega M et al (1997) Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-kappa B activation, monocyte chemoattractant protein-i expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis. Circulation 95:1532–1541

    CAS  PubMed  Google Scholar 

  283. Mancini GB (2000) Long-term use of angiotensin-converting enzyme inhibitors to modify endothelial dysfunction: a review of clinical investigations. Clin Invest Med 23:144–161

    CAS  PubMed  Google Scholar 

  284. O’Driscoll G, Green D, Maiorana A, Stanton K, Colreavy F, Taylor R (1999) Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. J Am Coll Cardiol 33:1506–1511

    PubMed  Google Scholar 

  285. Mullen MJ, Clarkson P, Donald AE, Thomson H, Thorne SA, Powe AJ et al (1998) Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study. J Am Coll Cardiol 31:1330–1335

    CAS  PubMed  Google Scholar 

  286. Hirooka Y, Imaizumi T, Masaki H, Ando S, Harada S, Momohara M et al (1992) Captopril improves impaired endothelium-dependent vasodilation in hypertensive patients. Hypertension 20:175–180

    CAS  PubMed  Google Scholar 

  287. Mancini GB, Henry GC, Macaya C, O’Neill BJ, Pucillo AL, Carere RG et al (1996) Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 94:258–265

    CAS  PubMed  Google Scholar 

  288. Esper RJ, Machado R, Vilarino J, Cacharron JL, Ingino CA, Garcia Guinazu CA et al (2000) Endothelium-dependent responses in patients with hypercholesterolemic coronary artery disease under the effects of simvastatin and enalapril, either separately or combined. Am Heart J 140:684–689

    CAS  PubMed  Google Scholar 

  289. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators (see comments). N Engl J Med 342:145–153

    CAS  PubMed  Google Scholar 

  290. Anderson TJ, Elstein E, Haber H, Charbonneau F (2000) Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study). J Am Coll Cardiol 35:60–66

    CAS  PubMed  Google Scholar 

  291. Goodfriend TI, Elliott ME, Catt KJ (1996) Angiotensin receptors and their antagonists. N Engl J Med 334:1649–1654

    CAS  PubMed  Google Scholar 

  292. Burnier M, Brunner HR (2000) Angiotensin II receptor antagonists. Lancet 355:637–645

    CAS  PubMed  Google Scholar 

  293. Schiffrin EL, Park JB, Intengan HD, Touyz RM (2000) Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation 101:1653–1659

    CAS  PubMed  Google Scholar 

  294. Strawn WB, Chappell MC, Dean RH, Kivlighn S, Ferrario CM (2000) Inhibition of early atherogenesis by losartan in monkeys with diet-induced hypercholesterolemia. Circulation 101:1586–1593

    CAS  PubMed  Google Scholar 

  295. Prasad A, Tupas-Habib T, Schenke WH, Mincemoyer R, Panza JA, Waclawin MA et al (2000) Acute and chronic angiotensin-i receptor antagonism reverses endothelial dysfunction in atherosclerosis. Circulation 101:2349–2354

    CAS  PubMed  Google Scholar 

  296. Ghiadoni L, Virdis A, Magagna A, Taddei S, Salvetti A (2000) Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension 35:501–506

    CAS  PubMed  Google Scholar 

  297. Farquharson CA, Struthers AD (2000) Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 101:594–597

    CAS  PubMed  Google Scholar 

  298. Silber DH, Sinoway LI (1990) Reversible impairment of forearm vasodilation after forearm casting. J Appl Physiol 68:1945–1949

    CAS  PubMed  Google Scholar 

  299. Sinoway LI, Shenberger J, Wilson J, McLaughlin D, Musch T, Zelis R (1987) A 30-day forearm work protocol increases maximal forearm blood flow. J Appl Physiol 62:1063–1067

    CAS  PubMed  Google Scholar 

  300. Schuler G, Hambrecht R, Schlierf G, Niebauer J, Hauer K, Neumann J et al (1992) Regular physical exercise and low-fat diet. Effects on progression of coronary artery disease. Circulation 86:1–11

    CAS  PubMed  Google Scholar 

  301. Dorn J, Naughton J, Imamura D, Trevisan M (1999) Results of a multicenter randomized clinical trial of exercise and long-term survival in myocardial infarction patients: the National Exercise and Heart Disease Project (NEHDP). Circulation 100:1764–1769

    CAS  PubMed  Google Scholar 

  302. Manson JE, Hu FB, Rich-Edwards JW, Colditz GA, Stampfer MJ, Willett WC et al (1999) A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women. N Engl J Med 341:650–658

    CAS  PubMed  Google Scholar 

  303. Clarkson P, Montgomery HE, Mullen MJ, Donald AE, Powe AJ, Bull T et al (1999) Exercise training enhances endothelial function in young men. J Am Coll Cardiol 33:1379–1385

    CAS  PubMed  Google Scholar 

  304. Hambrecht R, Wolf A, Gielen S, Linke A, Hofer J, Erbs S et al (2000) Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med 342:454–460

    CAS  PubMed  Google Scholar 

  305. Taddei S, Galetta F, Virdis A, Ghiadoni L, Salvetti G, Franzoni F et al (2000) Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation 101:2896–2901

    CAS  PubMed  Google Scholar 

  306. DeSouza CA, Shapiro LF, Clevenger CM, Dinenno FA, Monahan KD, Tanaka H et al (2000) Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation 102:1351–1357

    CAS  PubMed  Google Scholar 

  307. Lewis TV, Dart AM, Chin-Dusting JP, Kingwell BA (1999) Exercise training increases basal nitric oxide production from the forearm in hyper-cholesterolemic patients. Arterioscler Thromb Vasc Biol 19:2782–2787

    CAS  PubMed  Google Scholar 

  308. Traverse JH, Wang YL, Du R, Nelson D, Lindstrom P, Archer SL et al (2000) Coronary nitric oxide production in response to exercise and endothelium-dependent agonists. Circulation 101:2526–2531

    CAS  PubMed  Google Scholar 

  309. Bergholm R, Makimattila S, Valkonen M, Liu ML, Lahdenpera S, Taskinen MR et al (1999) Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilatation in vivo. Atherosclerosis 145:341–349

    CAS  PubMed  Google Scholar 

  310. Landmesser U, Merten R, Spiekermann S, Büttner K, Drexler H, Hornig B (2000) Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 101:2264–2270

    CAS  PubMed  Google Scholar 

  311. Mügge A, Elwell JH, Peterson TE, Hofmeyer TG, Heistad DD, Harrison DG (1991) Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits. Circ Res 69:1293–1300

    PubMed  Google Scholar 

  312. Kugiyama K, Ohgushi M, Motoyama T, Hirashima O, Soejima H, Misumi K et al (1998) Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation. Circulation 97:2299–2301

    CAS  PubMed  Google Scholar 

  313. Vita JA, Frei B, Holbrook M, Gokce N, Leaf C, Keaney JF Jr (1998) L-2-oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction in patients with coronary artery disease. J Clin Invest 101:1408–1414

    CAS  PubMed Central  PubMed  Google Scholar 

  314. Nitenberg A, Paycha F, Ledoux S, Sachs R, Attali JR, Valensi P (1998) Coronary artery responses to physiological stimuli are improved by deferoxamine but not by L-arginine in non-insulin-dependent diabetic patients with angiographically normal coronary arteries and no other risk factors. Circulation 97:736–743

    CAS  PubMed  Google Scholar 

  315. Solzbach U, Hornig B, Jeserich M, Just H (1997) Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation 96:1513–1519

    CAS  PubMed  Google Scholar 

  316. Levine GN, Frei B, Koulouris SN, Gerhard MD, Keaney JFJ, Vita JA (1996) Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 93:1107–1113

    CAS  PubMed  Google Scholar 

  317. Ting HH, Timimi FK, Haley EA, Roddy MA, Ganz P, Craeger MA (1997) Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. Circulation 95:2617–2622

    CAS  PubMed  Google Scholar 

  318. Timimi FK, Ting HH, Haley EA, Roddy MA, Ganz P, Creager MA (1998) Vitamin C improves endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol 31:552–557

    CAS  PubMed  Google Scholar 

  319. Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A (1998) Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation 97:2222–2229

    CAS  PubMed  Google Scholar 

  320. Heller R, Unbehaun A, Schellenberg B, Mayer B, Werner-Felmayer G, Werner ER (2001) L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin. J Biol Chem 276:40–47

    CAS  PubMed  Google Scholar 

  321. Huang A, Vita JA, Venema RC, Keaney JF Jr (2000) Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem 275:17399–17406

    CAS  PubMed  Google Scholar 

  322. Abuja PM (1999) Ascorbate prevents prooxidant effects of urate in oxidation of human low-density lipoprotein. FEBS Lett 446:305–308

    CAS  PubMed  Google Scholar 

  323. Bowie AG, O’Neill LA (2000) Vitamin C inhibits NF-kappa B activation by TNF via the activation of P38 mitogen-activated protein kinase. J Immunol 165:7180–7188

    CAS  PubMed  Google Scholar 

  324. Gokce N, Keaney JF Jr, Frei B, Holbrook M, Olesiak M, Zachariah BJ et al (1999) Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 99:3234–3240

    CAS  PubMed  Google Scholar 

  325. Kinlay S, Fang JC, Hikita H, Ho I, Delagrange DM, Frei B et al (1999) Plasma alpha-tocopherol and coronary endothelium-dependent vasodilator function. Circulation 100:219–221

    CAS  PubMed  Google Scholar 

  326. Kugiyama K, Motoyama T, Doi H, Kawano H, Hirai N, Soejima H et al (1999) Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoprotein levels. J Am Coll Cardiol 33:1512–1518

    CAS  PubMed  Google Scholar 

  327. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P (2000) Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342:154–160

    CAS  PubMed  Google Scholar 

  328. Carr AC, Zhu BZ, Frei B (2000) Potential antiatherogenic mechanisms of ascorbate (vitamin C) and alpha-tocopherol (vitamin E). Circ Res 87:349–354

    CAS  PubMed  Google Scholar 

  329. Neunteufl T, Priglinger U, Heher S, Zehetgruber M, Soregi G, Lehr S et al (2000) Effects of vitamin E on chronic and acute endothelial dysfunction in smokers. J Am Coll Cardiol 35:277–283

    CAS  PubMed  Google Scholar 

  330. Patterson C, Madamanchi NR, Runge MS (2000) The oxidative paradox: another piece in the puzzle. Circ Res 87:1074–1076

    CAS  PubMed  Google Scholar 

  331. Butler R, Morris AD, Belch JJF, Hill A, Struthers AD (2000) Allopurinol normalizes endothelial dysfunction in type 2 diabetic with mild hypertension. Hypertension 35:746–751

    CAS  PubMed  Google Scholar 

  332. Cardillo C, Kilcoyne CM, Cannon RO III, Quyyumi AA, Panza JA (1997) Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator function in hypercholesterolemic but not in hypertensive patients. Hypertension 30:57–63

    CAS  PubMed  Google Scholar 

  333. Verhaar MC, Strachan FE, Newby DE, Cruden NL, Koomans HA, Rabelink TJ et al (1998) Endothelin-A receptor antagonist-mediated vasodilation is attenuated by inhibition of nitric oxide synthesis and by endothelin-B-receptor blockade. Circulation 97:752–756

    CAS  PubMed  Google Scholar 

  334. Cardillo C, Kilcoyne CM, Cannon RO III, Panza JA (2000) Increased activity of endogenous endothelin in patients with hypercholesterolemia. J Am Coll Cardiol 36:1483–1488

    CAS  PubMed  Google Scholar 

  335. Cardillo C, Kilcoyne CM, Waclawiw M, Cannon RO III, Panza JA (1999) Role of endothelin in the increased vascular tone of patients with essential hypertension. Hypertension 33:753–758

    CAS  PubMed  Google Scholar 

  336. Kyriakides ZS, Kremastinos DT, Bofilis E, Tousoulis D, Antoniadis A, Webb DJ (2000) Endogenous endothelin maintains coronary artery tone by endothelin type A receptor stimulation in patients undergoing coronary arteriography. Heart 84:176–182

    CAS  PubMed Central  PubMed  Google Scholar 

  337. Wenzel RR, Fleisch M, Shaw S, Noll G, Kaufmann U, Schmitt R et al (1998) Hemodynamic and coronary effects of the endothelin antagonist bosentan in patients with coronary artery disease. Circulation 98:2235–2240

    CAS  PubMed  Google Scholar 

  338. Kinlay S, Behrendt D, Wainstein MV, Beltrame JF, Fang JC, Creager MA, Selwyn AP, Ganz P (2000) Endothelin-i enhances constrictor tone in atherosclerotic coronary arteries in humans (abstract). Circulation 102:11170

    Google Scholar 

  339. Bauersachs J, Fraccarollo D, Galuppo P, Widder J, Ertl G (2000) Endothelin-receptor blockade improves endothelial vasomotor dysfunction in heart failure. Cardiovasc Res 47:142–149

    CAS  PubMed  Google Scholar 

  340. Barton M, D’Uscio LV, Shaw S, Meyer P, Moreau P, Lüscher TF (1998) ETA receptor blockade prevents increased tissue endothelin-1, vascular hypertrophy, and endothelial dysfunction in salt-sensitive hypertension. Hypertension 31:499–504

    CAS  PubMed  Google Scholar 

  341. McKenna CJ, Burke SE, Opgenorth TJ, Padley RJ, Camrud LJ, Camrud AR et al (1998) Selective ETA receptor antagonism reduces neointimal hyperplasia in a porcine coronary stent model. Circulation 97:2551–2556

    CAS  PubMed  Google Scholar 

  342. Furberg CD, Psaty BM, Meyer JV (1995) Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. Circulation 92:1326–1331

    CAS  PubMed  Google Scholar 

  343. Pahor M, Psaty BM, Alderman MH, Applegate WB, Williamson JD, Cavazzini C et al (2000) Health outcomes associated with calcium antagonists compared with other first-line antihypertensive therapies: a meta-analysis of randomised trials. Lancet 356:1949–1954

    CAS  PubMed  Google Scholar 

  344. Pitt B, Byington RP, Furberg CD, Hunninghake DB, Mancini GB, Miller ME et al (2000) Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. Circulation 102:1503–1510

    CAS  PubMed  Google Scholar 

  345. Jukema JW, Zwinderman AH, Van Boven AJ, Reiber JHC, Van der Laarse A, Lie Kl et al (1996) Evidence for a synergistic effect of calcium channel blockers with lipid-lowering therapy in retarding progression of coronary atherosclerosis in symptomatic patients with normal to moderately raised cholesterol levels. Arterioscler Thromb Vasc Biol 16:425–430

    CAS  PubMed  Google Scholar 

  346. Lüscher TF, Yang Z (1993) Calcium antagonists and ACE inhibitors. Effect on endothelium and vascular smooth muscle. Drugs 46:121–132

    PubMed  Google Scholar 

  347. Lüscher TF, Zeiher AM, Meinertz T, Hugenholtz G, Quitzau K, Jenni R et al (1997) Effects of calcium antagonism and HMG-CoA-enzyme reductase inhibition on endothelial function and atherosclerosis: rationale and outline of the ENCORE trials. J Cardiovasc Pharmacol 30:848–852

    Google Scholar 

  348. Schächinger V, Zeiher AM (1997) NO in der Therapie der Angina pectoris: Nitrate oder Molsidomin? Internist 38:438–447

    PubMed  Google Scholar 

  349. Brown BG, Bolson E, Peterson RB, Pierce CD, Dodge HG (1981) The mechanism of nitroglycerin action: stenosis vasodilation as a major component of the drug response. Circulation 64:1089–1097

    CAS  PubMed  Google Scholar 

  350. Dendorfer A (1996) Pharmakologie der Nitrate und anderer NO-Donatoren. Herz 21:38–49

    PubMed  Google Scholar 

  351. Münzel T, Hink U, Yigit H, Macharzina R, Harrison DG, Mulsch A (1999) Role of Superoxide dismutase in in vivo and in vitro nitrate tolerance. Br J Pharmacol 127:1224–1230

    PubMed Central  PubMed  Google Scholar 

  352. Kurz S, Hink U, Nickenig G, Borthayre AB, Harrison DG, Munzel T (1999) Evidence for a causal role of the renin-angiotensin system in nitrate tolerance. Circulation 99:3181–3187

    CAS  PubMed  Google Scholar 

  353. Münzel T, Li H, Mollnau H, Hink U, Matheis E, Hartmann M et al (2000) Effects of long-term nitroglycerin treatment on endothelial nitric oxide synthase (NOS III) gene expression, NOS Ill-mediated superoxide production, and vascular NO bioavailability. Circ Res 86:E7-E12

    Google Scholar 

  354. Münzel T, Kurz S, Rajagopalan S, Thoenes M, Berrington WR, Thompson JA et al (1996) Hydralazine prevents nitroglycerin tolerance by inhibiting activation of a membrane-bound NADH oxidase — a new action for an old drug. J Clin Invest 98:1465–1470

    PubMed Central  PubMed  Google Scholar 

  355. Watanabe H, Kakihana M, Ohtsuka S, Sugishita Y (1997) Randomized, double-blind, placebo-controlled study of supplemental vitamin E on attenuation of the development of nitrate tolerance. Circulation 96:2545–2550

    CAS  PubMed  Google Scholar 

  356. Heitzer T, Just H, Brockhoff C, Meinertz T, Olschewski M, Munzel T (1998) Long-term nitroglycerin treatment is associated with supersensitivity to vasoconstrictors in men with stable coronary artery disease: prevention by concomitant treatment with Captopril. J Am Coll Cardiol 31:83–88

    CAS  PubMed  Google Scholar 

  357. Münzel T, Mollnau H, Hartmann M, Geiger C, Oelze M, Warnholtz A et al (2000) Effects of a nitrate-free interval on tolerance, vasoconstrictor sensitivity and vascular superoxide production. J Am Coll Cardiol 36:628–634

    PubMed  Google Scholar 

  358. Gruppo Italiano per lo Studio della Soprawivenza nell’infarto Miocardico (1994) GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet 343:1115–1122

    Google Scholar 

  359. ISIS-4 Collaborative Group (1995) ISIS-4: a randomised factorial trial assessing early oral Captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS 4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet 345:669–685

    Google Scholar 

  360. Gilligan DM, Badar DM, Panza JA, Quyyumi AA, Cannon RO III (1994) Acute vascular effects of estrogen in postmenopausal women. Circulation 90:786–791

    CAS  PubMed  Google Scholar 

  361. Reis SE, Gloth ST, Blumenthal RS, Resar JR, Zacur HA, Gerstenblith G (1994) Ethinyl estradiol acutely attenuates abnormal vasomotor responses to acetylcholine in postmenopausal women. Circulation 89:52–60

    CAS  PubMed  Google Scholar 

  362. Webb CM, Ghatei MA, McNeill JG, Collins P (2000) 17beta-estradiol decreases endothelin-1 levels in the coronary circulation of postmenopausal women with coronary artery disease. Circulation 102:1617–1622

    CAS  PubMed  Google Scholar 

  363. Koh KK, Cardillo C, Bui MN, Hathaway L, Csako G, Waclawiw MA et al (1999) Vascular effects of estrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women. Circulation 99:354–360

    CAS  PubMed  Google Scholar 

  364. Koh KK, Blum A, Hathaway L, Mincemoyer R, Csako G, Waclawiw MA et al (1999) Vascular effects of estrogen and vitamin E therapies in postmenopausal women. Circulation 100:1851–1857

    CAS  PubMed  Google Scholar 

  365. Guetta V, Quyyumi AA, Prasad A, Panza JA, Waclawiw M, Cannon RO 3rd (1997) The role of nitric oxide in coronary vascular effects of estrogen in postmenopausal women. Circulation 96:2795–2801

    CAS  PubMed  Google Scholar 

  366. Russell KS, Haynes MP, Caulin-Glaser T, Rosneck J, Sessa WC, Bender JR (2000) Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells. Effects on calcium sensitivity and NO release. J Biol Chem 275:5026–5030

    CAS  PubMed  Google Scholar 

  367. Hisamoto K, Ohmichi M, Kurachi H, Hayakawa J, Kanda Y, Nishio Y et al (2001) Estrogen induces the Akt-dependent activation of endothelial nitric-oxide synthase in vascular endothelial cells. J Biol Chem 276:3459–3467

    CAS  PubMed  Google Scholar 

  368. Goetz RM, Thatte HS, Prabhakar P, Cho MR, Michel T, Golan DE (1999) Estradiol induces the calcium-dependent translocation of endothelial nitric oxide synthase. Proc Natl Acad Sci USA 96:2788–2793

    CAS  PubMed Central  PubMed  Google Scholar 

  369. Virdis A, Ghiadoni L, Pinto S, Lombardo M, Petraglia F, Gennazzani A et al (2000) Mechanisms responsible for endothelial dysfunction associated with acute estrogen deprivation in normotensive women. Circulation 101:2258–2263

    CAS  PubMed  Google Scholar 

  370. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B et al (1998) Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 280:605–613

    CAS  PubMed  Google Scholar 

  371. Ridker PM, Hennekens CH, Rifai N, Buring JE, Manson JE (1999) Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 100:713–716

    CAS  PubMed  Google Scholar 

  372. Vehkavaara S, Hakala-Ala-Pietila T, Virkamaki A, Bergholm R, Ehnholm C, Hovatta O et al (2000) Differential effects of oral and transdermal estrogen replacement therapy on endothelial function in postmenopausal women. Circulation 102:2687–2693

    CAS  PubMed  Google Scholar 

  373. Williams JK, Adams MR (1997) Estrogens, progestins and coronary artery reactivity. Certain progestins may oppose the favorable effect of estrogen on the cardiovascular system of postmenopausal women. Nature Med 3:273–274

    CAS  PubMed  Google Scholar 

  374. Hjalmarson A, Olsson G (1991) Myocardial infarction. Effects of β-blockade. Circulation 84:VI101–VI107

    Google Scholar 

  375. Gaglione A, Hess OM, Corin WJ et al (1987) Is there coronary vasoconstriction after by beta-adrenergic blockade in patients with coronary artery disease? J Am Coll Cardiol 10:299–310

    CAS  PubMed  Google Scholar 

  376. Lopez BL, Christopher TA, Yue TL, Ruffolo R, Feuerstein GZ, Ma XL (1995) Carvedilol, a new beta-adrenoreceptor blocker antihypertensive drug, protects against free-radical-induced endothelial dysfunction. Pharmacology 51:165–173

    CAS  PubMed  Google Scholar 

  377. Broeders MA, Doevendans PA, Bekkers BC, Bronsaer R, van Gorsel E, Heemskerk JW et al (2000) Nebivolol: a third-generation beta-blocker that augments vascular nitric oxide release: endothelial beta(2)-adrenergic receptor-mediated nitric oxide production. Circulation 102:677–684

    CAS  PubMed  Google Scholar 

  378. Garlichs CD, Zhang H, Mugge A, Daniel WG (1999) Beta-blockers reduce the release and synthesis of endothelin-i in human endothelial cells. Eur J Clin Invest 29:12–16

    CAS  PubMed  Google Scholar 

  379. Matsuda Y, Akita H, Terashima M, Shiga N, Kanazawa K, Yoko-yama M (2000) Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease. Am Heart J 140: 753–759

    CAS  PubMed  Google Scholar 

  380. Kukin ML, Kaiman J, Charney RH, Levy DK, Buchholz-Varley C, Ocampo ON et al (1999) Prospective, randomized comparison of effect of long-term treatment with metoprolol or Carvedilol on symptoms, exercise, ejection fraction, and oxidative stress in heart failure. Circulation 99:2645–2651

    CAS  PubMed  Google Scholar 

  381. Ross R (1999) Atherosclerosis — an inflammatory disease. N Engl J Med 340:115–126

    CAS  PubMed  Google Scholar 

  382. Raza K, Thambyrajah J, Townend JN, Exley AR, Hortas C, Filer A et al (2000) Suppression of inflammation in primary systemic vasculitis restores vascular endothelial function: lessons for atherosclerotic disease? Circulation 102:1470–1472

    CAS  PubMed  Google Scholar 

  383. Azar RR, Rinfret S, Theroux P, Stone PH, Dakshinamurthy R, Feng YJ et al (2000) A randomized placebo-controlled trial to assess the efficacy of antiinflammatory therapy with methylpred-nisolone in unstable angina (MUNA trial). Eur Heart J 21:2026–2032

    CAS  PubMed  Google Scholar 

  384. Ikonomidis I, Andreotti F, Economou E, Stefanadis C, Toutouzas P, Nihoyannopoulos P (1999) Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 100:793–798

    CAS  PubMed  Google Scholar 

  385. Awtry EH, Loscalzo J (2000) Aspirin. Circulation 101:1206–1218

    CAS  PubMed  Google Scholar 

  386. Smith CJ, Zhang Y, Koboldt CM et al (1998) Pharmacological analysis of cyclooxygenase-i in inflammation. Proc Natl Acad Sci USA 95:13313–13318

    CAS  PubMed Central  PubMed  Google Scholar 

  387. Belton O, Byrne D, Kearney D, Leahy A, Fitzgerald DJ (2000) Cyclo-oxygenase-i and-2-dependent prostacyclin formation in patients with atherosclerosis. Circulation 102:840–845

    CAS  PubMed  Google Scholar 

  388. Duffy SJ, Tran BT, New G, Tudball RN, Esler MD, Harper RW et al (1998) Continuous release of vasodilator prostanoids contributes to regulation of resting forearm blood flow in humans. Am J Physiol 274:H1174–H1183

    Google Scholar 

  389. Duffy SJ, New G, Tran BT, Harper RW, Meredith IT(1999) Relative contribution of vasodilator prostanoids and NO to metabolic vasodilation in the human forearm. Am J Physiol 276:H663–H670

    Google Scholar 

  390. Duffy SJ, Castle SF, Harper RW, Meredith IT (1999) Contribution of vasodilator prostanoids and nitric oxide to resting flow, metabolic vasodilation, and flow-mediated dilation in human coronary circulation. Circulation 100:1951–1957

    CAS  PubMed  Google Scholar 

  391. Husain S, Andrews NP, Mulcahy D, Panza JA, Quyyumi AA (1998) Aspirin improves endothelial dysfunction in atherosclerosis. Circulation 97:716–720

    CAS  PubMed  Google Scholar 

  392. Noon JP, Walker BR, Hand MF, Webb DJ (1998) Impairment of forearm vasodilatation to acetylcholine in hypercholesterolemia is reversed by aspirin. Cardiovasc Res 38:480–484

    CAS  PubMed  Google Scholar 

  393. Breuer S, Fichtischerer B, Britten MB (2000) High-dose aspirin profoundly improves endothelial dysfunction in patients with coronary artery disease receiving chronic low-dose aspirin treatment (abstract). Circulation 102:1156

    Google Scholar 

  394. FitzGerald GA, Smith B, Pedersen AK, Brash AR (1984) Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. N Engl J Med 310:1065–1068

    Google Scholar 

  395. Hingorani AD, Cross J, Kharbanda RK, Mullen MJ, Bhagat K, Taylor M et al (2000) Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation 102:994–999

    CAS  PubMed  Google Scholar 

  396. Camm AJ, Fox KM (2000) Chlamydia pneumonia (and other infective agents) in atherosclerosis and acute coronary syndromes. How good is the evidence? Eur Heart J 21:1046–1051

    CAS  PubMed  Google Scholar 

  397. Mehta JL, Romeo F (2000) Inflammation, infection and atherosclerosis: do antibacterials have a role in the therapy of coronary artery disease? Drugs 59:159–170

    CAS  PubMed  Google Scholar 

  398. Danesh J (1999) Coronary heart disease, helicobacter pylori, dental disease, chlamydia pneumoniae, and cytomegalovirus: meta-analyses of prospective studies. Am Heart J 138:8434–8437

    Google Scholar 

  399. Danesh J, Collins R, Peto R (1997) Chronic infections and coronary heart disease: is there a link? Lancet 350:430–436

    CAS  PubMed  Google Scholar 

  400. Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm AJ (1997) Elevated chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 96:404–407

    CAS  PubMed  Google Scholar 

  401. Gurfinkel E, Bozovich G, Daroca A, Beck E, Mautner B (1997) Randomized trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study. Lancet 350:404–407

    CAS  PubMed  Google Scholar 

  402. Muhlestein JB, Anderson JL, Carlquist JF, Salunkhe K, Hörne BD, Pearson RR et al (2000) Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study. Circulation 102:1755–1760

    CAS  PubMed  Google Scholar 

  403. Epstein SE, Zhu J, Burnett MS, Zhou YF, Vercellotti G, Hajjar D (2000) Infection and atherosclerosis: potential roles of pathogen burden and molecular mimicry (editorial). Arterioscler Thromb Vasc Biol 20:1417–1420

    CAS  PubMed  Google Scholar 

  404. Hajjar DP (2000) Oxidized lipoproteins and infectious agents: are they in collusion to accelerate atherogenesis? Arterioscler Thromb Vasc Biol 20:1421–1422

    CAS  PubMed  Google Scholar 

  405. Mayr M, Kiechl S, Willeit J, Wick G, Xu Q (2000) Infections, immunity, and atherosclerosis: associations of antibodies to chlamydia pneumoniae, helicobacter pylori, and cytomegalovirus with immune reactions to heat-shock protein 60 and carotid or femoral atherosclerosis. Circulation 102:833–839

    CAS  PubMed  Google Scholar 

  406. Hochleitner BW, Hochleitner EO, Obrist P, Eberl T, Amberger A, Xu Q et al (2000) Fluid shear stress induces heat shock protein 60 expression in endothelial cells in vitro and in vivo. Arterioscler Thromb Vasc Biol 20:617–623

    CAS  PubMed  Google Scholar 

  407. Xu Q, Schert G, Perschinka H, Mayr M, Egger G, Oberhollenzer F et al (2000) Serum soluble heat shock protein 60 is elevated in subjects with atherosclerosis in a general population. Circulation 102:14–20

    CAS  PubMed  Google Scholar 

  408. Pockley AG, Wu R, Lemne C, Kiessling R, De Faire U, Frostegard J (2000) Circulating heat shock protein 60 is associated with early cardiovascular disease. Hypertension 36:303–307

    CAS  PubMed  Google Scholar 

  409. Yla-Herttuala S, Martin JF (2000) Cardiovascular gene therapy. Lancet 355:213–222

    CAS  PubMed  Google Scholar 

  410. Kullo IJ, Mozes G, Schwartz RS, Gloviczki P, Crotty TB, Barber DA et al (1997) Adventitial gene transfer of recombinant endothelial nitric oxide synthase to rabbit carotid arteries alters vascular reactivity. Circulation 96:2254–2261

    CAS  PubMed  Google Scholar 

  411. Horowitz JR, Rivard A, van der ZR, Hariawala M, Sheriff DD, Esakof DD et al (1997) Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension. Evidence for a maintenance role in quiescent adult endothelium. Arterioscler Thromb Vasc Biol 17:2793–2800

    CAS  PubMed  Google Scholar 

  412. Marban E (2000) Gene therapy for common acquired diseases of the heart: the Sirens’ song (editorial). Circulation 101:1498–1499

    CAS  PubMed  Google Scholar 

  413. Schächinger V, Zeiher AM (1996) Importance of the endothelium for regulation of coronary vasomotor tone (in German). Z Kardiol 83:263–267

    Google Scholar 

  414. Britten MB, Schächinger V (1998) Role of endothelial function for ischemic manifestation of coronary artery disease (in German). Herz 23:97–105

    CAS  PubMed  Google Scholar 

  415. Schächinger V, Zeiher AM (2000) Atherosclerosis-associated endothelial dysfunction. Z Kardiol 89:1X70–1X74

    Google Scholar 

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Authors
  1. Volker Schächinger
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  2. Andreas M. Zeiher
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Editors and Affiliations

  1. Herz-Zentrum Coswig, Klinik für Kardiologie und Angiologie, Lerchenfeld 1, 06869, Coswig (Anhalt), Germany

    Peter Lanzer MD

  2. The Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, Cleveland, 44195, OH, USA

    Eric J. Topol MD

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Schächinger, V., Zeiher, A.M. (2002). Coronary Artery Disease and Endothelial Function. In: Lanzer, P., Topol, E.J. (eds) Pan Vascular Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56225-9_55

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  • DOI: https://doi.org/10.1007/978-3-642-56225-9_55

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