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Cardiovascular effects of leptin

Abstract

A wealth of investigations, ranging from clinical and animal model studies to in vitro analyses, have generated great interest in the cardiovascular effects of leptin. Accordingly, many studies have examined the contribution of leptin to cardiac remodeling in heart failure and whether the effects of leptin on metabolism, apoptosis, extracellular matrix remodeling, and hypertrophy could explain the so-called obesity paradox. Furthermore, obesity and hyperleptinemia have often been associated with hypertension, and regulation of sympathetic tone or direct effects of leptin on contributors such as atherosclerosis, endothelial dysfunction, and thrombosis have been documented. Unfortunately, translating basic research studies in vitro, or in animal models, to human physiology has proven difficult. The degree of leptin resistance in obesity is one intriguing issue that must be resolved. Furthermore, the importance of autocrine and paracrine effects of leptin derived from the heart and perivascular adipose tissue must be further studied. Carefully planned and executed research to conclusively establish distinct effects of leptin on the cardiovascular system in normal and diseased states will be essential to harness any therapeutic potential associated with leptin's effects.

Key Points

  • Leptin regulates various cardiovascular effects, yet many paradoxical observations have been reported and several controversies remain

  • Reasons for these discrepancies may include the temporal nature of cardiovascular disease, actual leptin concentration examined, and the degree of crosstalk with other cardioregulatory factors

  • Leptin resistance is thought to develop in obese individuals, yet may be selective to only a subset of the physiological effects of leptin

  • Excess or inadequate leptin signaling are likely to result in unfavorable outcomes, and the maintenance of homeostatic leptin effects may be a beneficial treatment strategy

  • The myocardium and perivascular adipose tissue are known sources of leptin, which might exert important autocrine and paracrine effects

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Figure 1: Altered leptin sensitivity and circulating levels of leptin in obese individuals.
Figure 2: Direct effects of leptin on the heart.
Figure 3: Direct effects of leptin on the vasculature.

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References

  1. Abel, E. D., Litwin, S. E. & Sweeney, G. Cardiac remodeling in obesity. Physiol. Rev. 88, 389–419 (2008).

    CAS  PubMed  Google Scholar 

  2. Sweeney, G. Unraveling the mechanisms linking obesity and heart failure: the role of adipokines. Expert Rev. Endocrinol. Metab. 4, 95–97 (2009).

    PubMed  Google Scholar 

  3. Rajapurohitam, V., Javadov, S., Purdham, D. M., Kirshenbaum, L. A. & Karmazyn, M. An autocrine role for leptin in mediating the cardiomyocyte hypertrophic effects of angiotensin II and endothelin-1. J. Mol. Cell. Cardiol. 41, 265–274 (2006).

    CAS  PubMed  Google Scholar 

  4. Purdham, D. M., Zou, M. X., Rajapurohitam, V. & Karmazyn, M. Rat heart is a site of leptin production and action. Am. J. Physiol. Heart Circ. Physiol. 287, H2877–H2884 (2004).

    CAS  PubMed  Google Scholar 

  5. Cheng, K. H. et al. Adipocytokines and proinflammatory mediators from abdominal and epicardial adipose tissue in patients with coronary artery disease. Int. J. Obes. (Lond.) 32, 268–274 (2008).

    CAS  Google Scholar 

  6. Rabkin, S. W. Epicardial fat: properties, function and relationship to obesity. Obes. Rev. 8, 253–261 (2007).

    CAS  PubMed  Google Scholar 

  7. Silaghi, A. et al. Epicardial adipose tissue extent: relationship with age, body fat distribution, and coronaropathy. Obesity (Silver Spring) 16, 2424–2430 (2008).

    Google Scholar 

  8. Sarin, S. et al. Clinical significance of epicardial fat measured using cardiac multislice computed tomography. Am. J. Cardiol. 102, 767–771 (2008).

    PubMed  Google Scholar 

  9. Iacobellis, G. et al. Influence of excess fat on cardiac morphology and function: study in uncomplicated obesity. Obes. Res. 10, 767–773 (2002).

    PubMed  Google Scholar 

  10. Iacobellis, G. & Leonetti, F. Epicardial adipose tissue and insulin resistance in obese subjects. J. Clin. Endocrinol. Metab. 90, 6300–6302 (2005).

    CAS  PubMed  Google Scholar 

  11. Kim, M. K. et al. Aerobic exercise training reduces epicardial fat in obese men. J. Appl. Physiol. 106, 5–11 (2009).

    PubMed  Google Scholar 

  12. Willens, H. J. et al. Effects of weight loss after bariatric surgery on epicardial fat measured using echocardiography. Am. J. Cardiol. 99, 1242–1245 (2007).

    PubMed  Google Scholar 

  13. Iacobellis, G., Singh, N., Wharton, S. & Sharma, A. M. Substantial changes in epicardial fat thickness after weight loss in severely obese subjects. Obesity (Silver Spring) 16, 1693–1697 (2008).

    Google Scholar 

  14. Iacobellis, G., Gao, Y. J. & Sharma, A. M. Do cardiac and perivascular adipose tissue play a role in atherosclerosis? Curr. Diab. Rep. 8, 20–24 (2008).

    PubMed  Google Scholar 

  15. Stern, N. & Marcus, Y. Perivascular fat: innocent bystander or active player in vascular disease? J. Cardiometab. Syndr. 1, 115–120 (2006).

    PubMed  Google Scholar 

  16. Knudson, J. D., Payne, G. A., Borbouse, L. & Tune, J. D. Leptin and mechanisms of endothelial dysfunction and cardiovascular disease. Curr. Hypertens. Rep. 10, 434–439 (2008).

    CAS  PubMed  Google Scholar 

  17. Barandier, C., Montani, J. P. & Yang, Z. Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity. Am. J. Physiol. Heart Circ. Physiol. 289, H1807–H1813 (2005).

    CAS  PubMed  Google Scholar 

  18. Ahima, R. S. & Flier, J. S. Leptin. Annu. Rev. Physiol. 62, 413–437 (2000).

    CAS  PubMed  Google Scholar 

  19. Martin, S. S., Qasim, A. & Reilly, M. P. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J. Am. Coll. Cardiol. 52, 1201–1210 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Enriori, P., Evans, A. E., Sinnayah, P. & Cowley, M. A. Leptin resistance and obesity. Obesity (Silver Spring) 14, 254S–258S (2006).

    CAS  Google Scholar 

  21. Koh, K. K., Park, S. M. & Quon, M. J. Leptin and cardiovascular disease: response to therapeutic interventions. Circulation 117, 3238–3249 (2008).

    PubMed  PubMed Central  Google Scholar 

  22. Buchanan, J. et al. Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity. Endocrinology 146, 5341–5349 (2005).

    CAS  PubMed  Google Scholar 

  23. Christoffersen, C. et al. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology 144, 3483–3490 (2003).

    CAS  PubMed  Google Scholar 

  24. Semeniuk, L. M., Kryski, A. J. & Severson, D. L. Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice. Am. J. Physiol. Heart Circ. Physiol. 283, H976–H982 (2002).

    CAS  PubMed  Google Scholar 

  25. Young, M. E. et al. Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart. Diabetes 51, 2587–2595 (2002).

    CAS  PubMed  Google Scholar 

  26. Konstantinides, S., Schafer, K., Koschnick, S. & Loskutoff, D. J. Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. J. Clin. Invest. 108, 1533–1540 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Bodary, P. F., Westrick, R. J., Wickenheiser, K. J., Shen, Y. & Eitzman, D. T. Effect of leptin on arterial thrombosis following vascular injury in mice. JAMA 287, 1706–1709 (2002).

    CAS  PubMed  Google Scholar 

  28. Beltowski, J. Leptin and atherosclerosis. Atherosclerosis 189, 47–60 (2006).

    CAS  PubMed  Google Scholar 

  29. Bell-Anderson, K. S. & Bryson, J. M. Leptin as a potential treatment for obesity: progress to date. Treat. Endocrinol. 3, 11–18 (2004).

    CAS  PubMed  Google Scholar 

  30. Correia, M. L. & Rahmouni, K. Role of leptin in the cardiovascular and endocrine complications of metabolic syndrome. Diabetes Obes. Metab. 8, 603–610 (2006).

    CAS  PubMed  Google Scholar 

  31. Hintz, K. K., Aberle, N. S. & Ren, J. Insulin resistance induces hyperleptinemia, cardiac contractile dysfunction but not cardiac leptin resistance in ventricular myocytes. Int. J. Obes. Relat. Metab. Disord. 27, 1196–1203 (2003).

    CAS  PubMed  Google Scholar 

  32. Lopaschuk, G. D., Folmes, C. D. & Stanley, W. C. Cardiac energy metabolism in obesity. Circ. Res. 101, 335–347 (2007).

    CAS  PubMed  Google Scholar 

  33. Atkinson, L. L., Fischer, M. A. & Lopaschuk, G. D. Leptin activates cardiac fatty acid oxidation independent of changes in the AMP-activated protein kinase-acetyl-CoA carboxylase-malonyl-CoA axis. J. Biol. Chem. 277, 29424–29430 (2002).

    CAS  PubMed  Google Scholar 

  34. Sharma, V. et al. Stimulation of cardiac fatty acid oxidation by leptin is mediated by a nitric oxide-p38 MAPK-dependent mechanism. Eur. J. Pharmacol. 617, 113–117 (2009).

    CAS  PubMed  Google Scholar 

  35. Palanivel, R., Eguchi, M., Shuralyova, I., Coe, I. & Sweeney, G. Distinct effects of short- and long-term leptin treatment on glucose and fatty acid uptake and metabolism in HL-1 cardiomyocytes. Metabolism 55, 1067–1075 (2006).

    CAS  PubMed  Google Scholar 

  36. Berk, P. D. et al. Uptake of long chain free fatty acids is selectively up-regulated in adipocytes of Zucker rats with genetic obesity and non-insulin-dependent diabetes mellitus. J. Biol. Chem. 272, 8830–8835 (1997).

    CAS  PubMed  Google Scholar 

  37. Luiken, J. J. et al. Increased rates of fatty acid uptake and plasmalemmal fatty acid transporters in obese Zucker rats. J. Biol. Chem. 276, 40567–40573 (2001).

    CAS  PubMed  Google Scholar 

  38. Sharma, S. et al. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J. 18, 1692–1700 (2004).

    CAS  PubMed  Google Scholar 

  39. McGavock, J. M., Victor, R. G., Unger, R. H. & Szczepaniak, L. S. Adiposity of the heart, revisited. Ann. Intern. Med. 144, 517–524 (2006).

    CAS  PubMed  Google Scholar 

  40. Szczepaniak, L. S. et al. Myocardial triglycerides and systolic function in humans: in vivo evaluation by localized proton spectroscopy and cardiac imaging. Magn. Reson. Med. 49, 417–423 (2003).

    CAS  PubMed  Google Scholar 

  41. Mazumder, P. K. et al. Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes 53, 2366–2374 (2004).

    CAS  PubMed  Google Scholar 

  42. Kamohara, S., Burcelin, R., Halaas, J. L., Friedman, J. M. & Charron, M. J. Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389, 374–377 (1997).

    CAS  PubMed  Google Scholar 

  43. Haap, M. et al. Insulin-like effect of low-dose leptin on glucose transport in Langendorff rat hearts. Exp. Clin. Endocrinol. Diabetes 111, 139–145 (2003).

    CAS  PubMed  Google Scholar 

  44. Wang, P., Lloyd, S. G., Zeng, H., Bonen, A. & Chatham, J. C. Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats. Am. J. Physiol. Heart Circ. Physiol. 288, H2102–H2110 (2005).

    CAS  PubMed  Google Scholar 

  45. Golfman, L. S. et al. Activation of PPARgamma enhances myocardial glucose oxidation and improves contractile function in isolated working hearts of ZDF rats. Am. J. Physiol. Endocrinol. Metab. 289, E328–E336 (2005).

    CAS  PubMed  Google Scholar 

  46. Lee, Y. & Gustafsson, A. B. Role of apoptosis in cardiovascular disease. Apoptosis 14, 536–548 (2009).

    PubMed  Google Scholar 

  47. Narula, J. et al. Apoptosis in myocytes in end-stage heart failure. N. Engl. J. Med. 335, 1182–1189 (1996).

    CAS  PubMed  Google Scholar 

  48. Olivetti, G. et al. Apoptosis in the failing human heart. N. Engl. J. Med. 336, 1131–1141 (1997).

    CAS  PubMed  Google Scholar 

  49. Todor, A. et al. Hypoxia-induced cleavage of caspase-3 and DFF45/ICAD in human failed cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 283, H990–H995 (2002).

    CAS  PubMed  Google Scholar 

  50. Sung, M. M. et al. Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. J. Mol. Cell. Cardiol. 43, 429–436 (2007).

    CAS  PubMed  Google Scholar 

  51. Communal, C. et al. Functional consequences of caspase activation in cardiac myocytes. Proc. Natl Acad. Sci. USA 99, 6252–6256 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Shin, E. J., Schram, K., Zheng, X. L. & Sweeney, G. Leptin attenuates hypoxia/reoxygenation-induced apoptosis in rat H9c2 cardiomyocytes. J. Cell. Physiol. (in press).

  53. Eguchi, M., Liu, Y., Shin, E. J. & Sweeney, G. Leptin protects H9c2 rat cardiomyocytes from H2O2-induced apoptosis. FEBS J. 275, 3136–3144 (2008).

    CAS  PubMed  Google Scholar 

  54. McGaffin, K. R., Zou, B., McTiernan, C. F. & O'Donnell, C. P. Leptin attenuates cardiac apoptosis after chronic ischaemic injury. Cardiovasc. Res. 83, 313–324 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Barouch, L. et al. Cardiac myocytes apopotosis is associated with increased DNA damage and decreased survival in murine models of obesity. Circ. Res. 98, 119–124 (2006).

    CAS  PubMed  Google Scholar 

  56. Trivedi, P., Yang, R. & Barouch, L. A. Decreased p110alpha catalytic activity accompanies increased myocyte apoptosis and cardiac hypertrophy in leptin deficient ob/ob mice. Cell Cycle 7, 560–565 (2008).

    CAS  PubMed  Google Scholar 

  57. Smith, C. C. et al. Leptin, the obesity-associated hormone, exhibits direct cardioprotective effects. Br. J. Pharmacol. 149, 5–13 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhou, Y. T. et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc. Natl Acad. Sci. USA 97, 1784–1789 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Dixon, R. A., Davidson, S. M., Wynne, A. M., Yellon, D. M. & Smith, C. C. The cardioprotective actions of leptin are lost in the Zucker obese (fa/fa) rat. J. Cardiovasc. Pharmacol. 53, 311–317 (2009).

    CAS  PubMed  Google Scholar 

  60. Florea, V. G. et al. Left ventricular remodelling: common process in patients with different primary myocardial disorders. Int. J. Cardiol. 68, 281–287 (1999).

    CAS  PubMed  Google Scholar 

  61. Cohn, J. N. Structural basis for heart failure. Ventricular remodeling and its pharmacological inhibition. Circulation 91, 2504–2507 (1995).

    CAS  PubMed  Google Scholar 

  62. Frey, N. & Olson, E. N. Cardiac hypertrophy: the good, the bad, and the ugly. Annu. Rev. Physiol. 65, 45–79 (2003).

    CAS  PubMed  Google Scholar 

  63. Frey, N., Katus, H. A., Olson, E. N. & Hill, J. A. Hypertrophy of the heart: a new therapeutic target? Circulation 109, 1580–1589 (2004).

    PubMed  Google Scholar 

  64. Madani, S., De Girolamo, S., Munoz, D. M., Li, R. K. & Sweeney, G. Direct effects of leptin on size and extracellular matrix components of human pediatric ventricular myocytes. Cardiovasc. Res. 69, 716–725 (2006).

    CAS  PubMed  Google Scholar 

  65. Rajapurohitam, V., Gan, X. T., Kirshenbaum, L. A. & Karmazyn, M. The obesity-associated peptide leptin induces hypertrophy in neonatal rat ventricular myocytes. Circ. Res. 93, 277–279 (2003).

    CAS  PubMed  Google Scholar 

  66. Xu, F. P. et al. Leptin induces hypertrophy via endothelin-1-reactive oxygen species pathway in cultured neonatal rat cardiomyocytes. Circulation 110, 1269–1275 (2004).

    CAS  PubMed  Google Scholar 

  67. Majumdar, P. et al. Leptin and endothelin-1 mediated increased extracellular matrix protein production and cardiomyocyte hypertrophy in diabetic heart disease. Diabetes Metab. Res. Rev. 25, 452–463 (2009).

    CAS  PubMed  Google Scholar 

  68. Zeidan, A., Javadov, S. & Karmazyn, M. Essential role of Rho/ROCK-dependent processes and actin dynamics in mediating leptin-induced hypertrophy in rat neonatal ventricular myocytes. Cardiovasc. Res. 72, 101–111 (2006).

    CAS  PubMed  Google Scholar 

  69. Zeidan, A., Javadov, S., Chakrabarti, S. & Karmazyn, M. Leptin-induced cardiomyocyte hypertrophy involves selective caveolae and RhoA/ROCK-dependent p38 MAPK translocation to nuclei. Cardiovasc. Res. 77, 64–72 (2008).

    CAS  PubMed  Google Scholar 

  70. Abe, Y. et al. Leptin induces elongation of cardiac myocytes and causes eccentric left ventricular dilatation with compensation. Am. J. Physiol. Heart Circ. Physiol. 292, H2387–H2396 (2007).

    CAS  PubMed  Google Scholar 

  71. Pinieiro, R. et al. Leptin does not induce hypertrophy, cell cycle alterations, or production of MCP-1 in cultured rat and mouse cardiomyocytes. Endocr. Res. 31, 375–386 (2005).

    PubMed  Google Scholar 

  72. Park, S. Y. et al. Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. Diabetes 54, 3530–3540 (2005).

    CAS  PubMed  Google Scholar 

  73. Purdham, D. M. et al. A neutralizing leptin receptor antibody mitigates hypertrophy and hemodynamic dysfunction in the postinfarcted rat heart. Am. J. Physiol. Heart Circ. Physiol. 295, H441–H446 (2008).

    CAS  PubMed  Google Scholar 

  74. Madani, S., De Girolamo, S., Muñoz, D. M., Li, R. K. & Sweeney, G. Direct effects of leptin on size and extracellular matrix components of human pediatric ventricular myocytes. Cardiovasc. Res. 69, 716–725 (2005).

    PubMed  Google Scholar 

  75. Wakatsuki, T., Schlessinger, J. & Elson, E. L. The biochemical response of the heart to hypertension and exercise. Trends Biochem. Sci. 29, 609–617 (2004).

    CAS  PubMed  Google Scholar 

  76. Dorn, G. W. 2nd & Force, T. Protein kinase cascades in the regulation of cardiac hypertrophy. J. Clin. Invest. 115, 527–537 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. McGaffin, K. R. et al. Leptin signalling reduces the severity of cardiac dysfunction and remodelling after chronic ischaemic injury. Cardiovasc. Res. 77, 54–63 (2008).

    CAS  PubMed  Google Scholar 

  78. Barouch, L. A., Berkowitz, D. E., Harrison, R. W., O'Donnell, C. P. & Hare, J. M. Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation 108, 754–759 (2003).

    CAS  PubMed  Google Scholar 

  79. Fedak, P., Verma, S., Weisel, R. D. & Li, R. K. Cardiac remodeling and failure: From molecules to man (Part II). Cardiovasc. Pathol. 14, 49–60 (2005).

    CAS  PubMed  Google Scholar 

  80. Fedak, P., Verma, S., Weisel, R. D. & Li, R. K. Cardiac remodeling and failure: from molecules to man (Part I). Cardiovasc. Pathol. 14, 1–11 (2005).

    PubMed  Google Scholar 

  81. Graham, H. K., Horn, M. & Trafford, A. W. Extracellular matrix profiles in the progression to heart failure. European Young Physiologists Symposium Keynote Lecture-Bratislava 2007. Acta Physiol. (Oxf.) 194, 3–21 (2008).

    CAS  Google Scholar 

  82. Schram, K. & Sweeney, G. Implications of myocardial matrix remodeling by adipokines in obesity-related heart failure. Trends Cardiovasc. Med. 18, 199–205 (2008).

    CAS  PubMed  Google Scholar 

  83. Schram, K. et al. Increased expression and cell surface localization of MT1-MMP plays a role in stimulation of MMP-2 activity by leptin in neonatal rat cardiac myofibroblasts. J. Mol. Cell. Cardiol. 44, 874–881 (2008).

    CAS  PubMed  Google Scholar 

  84. Zaman, A. K. et al. Angiotensin-converting enzyme inhibition attenuates hypofibrinolysis and reduces cardiac perivascular fibrosis in genetically obese diabetic mice. Circulation 103, 3123–3128 (2001).

    CAS  PubMed  Google Scholar 

  85. Zaman, A. K. et al. Salutary effects of attenuation of angiotensin II on coronary perivascular fibrosis associated with insulin resistance and obesity. J. Mol. Cell. Cardiol. 37, 525–535 (2004).

    CAS  PubMed  Google Scholar 

  86. Toblli, J. E., Cao, G., DeRosa, G. & Forcada, P. Reduced cardiac expression of plasminogen activator inhibitor 1 and transforming growth factor beta1 in obese Zucker rats by perindopril. Heart 91, 80–86 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Xia, Q. et al. Improvement of chronic heart failure by dexamehtason is not associated with downregulation of leptin in rats. Acta Pharmacologica Sinica 28, 202–210 (2007).

    CAS  PubMed  Google Scholar 

  88. Parish, R. C. & Evans, J. D. Inflammation in chronic heart failure. Ann. Pharmacother. 42, 1002–1016 (2008).

    CAS  PubMed  Google Scholar 

  89. Yndestad, A. et al. Role of inflammation in the progression of heart failure. Curr. Cardiol. Rep. 9, 236–241 (2007).

    PubMed  Google Scholar 

  90. Yndestad, A. et al. Systemic inflammation in heart failure--the whys and wherefores. Heart Fail. Rev. 11, 83–92 (2006).

    CAS  PubMed  Google Scholar 

  91. Chao, W. Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart. Am. J. Physiol. Heart Circ. Physiol. 296, H1–H12 (2009).

    CAS  PubMed  Google Scholar 

  92. Satoh, M., Ishikawa, Y., Minami, Y., Takahashi, Y. & Nakamura, M. Role of Toll like receptor signaling pathway in ischemic coronary artery disease. Front. Biosci. 13, 6708–6715 (2008).

    CAS  PubMed  Google Scholar 

  93. Batra, A. et al. Leptin-dependent toll-like receptor expression and responsiveness in preadipocytes and adipocytes. Am. J. Pathol. 170, 1931–1941 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Heymans, S. et al. Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology. Eur. J. Heart Fail. 11, 119–129 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Haynes, W. G. Role of leptin in obesity-related hypertension. Exp. Physiol. 90, 683–688 (2005).

    CAS  PubMed  Google Scholar 

  96. Rahmouni, K., Morgan, D. A., Morgan, G. M., Mark, A. L. & Haynes, W. G. Role of selective leptin resistance in diet-induced obesity hypertension. Diabetes 54, 2012–2018 (2005).

    CAS  PubMed  Google Scholar 

  97. Tumer, N., Erdos, B., Matheny, M., Cudykier, I. & Scarpace, P. J. Leptin antagonist reverses hypertension caused by leptin overexpression, but fails to normalize obesity-related hypertension. J. Hypertens. 25, 2471–2478 (2007).

    CAS  PubMed  Google Scholar 

  98. Su, W. et al. Hypertension and disrupted blood pressure circadian rhythm in type 2 diabetic db/db mice. Am. J. Physiol. Heart Circ. Physiol. 295, H1634–H1641 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Osmond, J. M., Mintz, J. D., Dalton, B. & Stepp, D. W. Obesity increases blood pressure, cerebral vascular remodeling, and severity of stroke in the Zucker rat. Hypertension 53, 381–386 (2009).

    CAS  PubMed  Google Scholar 

  100. Konstantinidis, D., Paletas, K., Koliakos, G. & Kaloyianni, M. Signaling components involved in leptin-induced amplification of the atherosclerosis-related properties of human monocytes. J. Vasc. Res. 46, 199–208 (2009).

    CAS  PubMed  Google Scholar 

  101. Korda, M., Kubant, R., Patton, S. & Malinski, T. Leptin-induced endothelial dysfunction in obesity. Am. J. Physiol. Heart Circ. Physiol. 295, H1514–H1521 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Knudson, J. D. et al. Leptin receptors are expressed in coronary arteries, and hyperleptinemia causes significant coronary endothelial dysfunction. Am. J. Physiol. Heart Circ. Physiol. 289, H48–H56 (2005).

    CAS  PubMed  Google Scholar 

  103. Procopio, C. et al. Leptin-stimulated endothelial nitric-oxide synthase via an adenosine 5′-monophosphate-activated protein kinase/Akt signaling pathway is attenuated by interaction with C-reactive protein. Endocrinology 150, 3584–3593 (2009).

    CAS  PubMed  Google Scholar 

  104. Knudson, J. D. et al. Leptin resistance extends to the coronary vasculature in prediabetic dogs and provides a protective adaptation against endothelial dysfunction. Am. J. Physiol. Heart Circ. Physiol. 289, H1038–H1046 (2005).

    CAS  PubMed  Google Scholar 

  105. Bodary, P. F. Links between adipose tissue and thrombosis in the mouse. Arterioscler. Thromb. Vasc. Biol. 27, 2284–2291 (2007).

    CAS  PubMed  Google Scholar 

  106. Nakata, M., Yada, T., Soejima, N. & Maruyama, I. Leptin promotes aggregation of human platelets via the long form of its receptor. Diabetes 48, 426–429 (1999).

    CAS  PubMed  Google Scholar 

  107. Dellas, C. et al. Absence of leptin resistance in platelets from morbidly obese individuals may contribute to the increased thrombosis risk in obesity. Thromb. Haemost. 100, 1123–1129 (2008).

    CAS  PubMed  Google Scholar 

  108. Elbatarny, H. S. & Maurice, D. H. Leptin-mediated activation of human platelets: involvement of a leptin receptor and phosphodiesterase 3A-containing cellular signaling complex. Am. J. Physiol. Endocrinol. Metab. 289, E695–E702 (2005).

    CAS  PubMed  Google Scholar 

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The author's work is funded by the Canadian Institutes of Health Research, Heart & Stroke Foundation of Canada, Canadian Diabetes Association and Korean Ministry of Education Science and Technology. Figures are intended to convey general conclusions from published literature and exceptions may exist.

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Sweeney, G. Cardiovascular effects of leptin. Nat Rev Cardiol 7, 22–29 (2010). https://doi.org/10.1038/nrcardio.2009.224

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