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Adaptation of a photochemical method to initiate recurrent platelet-mediated thrombosis in small animals

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Abstract

Platelet-mediated thrombosis represents the initial precipitating event in the genesis of unstable angina, acute myocardial infarction, and stroke. As a result, there is considerable interest in the preclinical discovery and screening of new ‘anti-platelet’ therapies aimed at limiting the incidence and reoccurrence of arterial thrombosis—efforts that, to date, have largely required the use of large animal models of thrombotic occlusion. In the current report, we describe the successful development of a small-animal (rat) model of spontaneous and recurrent platelet-mediated arterial thrombosis achieved by the in vivo administration of a photoactive dye (rose bengal) followed by focal illumination with green laser light.

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References

  1. American Heart Association: heart disease and stroke statistics—2006 update

  2. European cardiovascular disease statistics—2005 edition

  3. Becker RC (2000) Platelet surface physiology and its importance in pharmacotherapy design and development: the adenosine diphosphate receptor antagonists. J Thromb Thrombolysis 10:35–53

    Article  PubMed  CAS  Google Scholar 

  4. Cannon CP, Tracy R (1995) Clotting for the clinician: an overview of thrombosis and antithrombotic therapy. J Thromb Thrombolysis 2:95–106

    Article  PubMed  CAS  Google Scholar 

  5. Andrews RK, Berndt MC (2004) Platelet physiology and thrombosis. Thromb Res 114:447–453

    Article  PubMed  CAS  Google Scholar 

  6. Folts JD, Crowell EB Jr, Rowe GG (1976) Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation 54:365–370

    PubMed  CAS  Google Scholar 

  7. Folts J (1991) An in vivo model of experimental arterial stenosis, intimal damage, and periodic thrombosis. Circulation 83:IV3–IV14

    PubMed  CAS  Google Scholar 

  8. Ikeda H, Koga Y, Kuwano K, Nakayama H, Ueno T, Yoshida N, Adachi K, Park IS, Toshima H (1993) Cyclic flow variations in a conscious dog model of coronary artery stenosis and endothelial injury correlate with acute ischemic heart disease syndromes in humans. J Am Coll Cardiol 21:1008–1017

    Article  PubMed  CAS  Google Scholar 

  9. Hata K, Whittaker P, Kloner RA, Przyklenk K (1998) Brief antecedent ischemia attenuates platelet-mediated thrombosis in damaged and stenotic canine coronary arteries: role of adenosine. Circulation 97:692–702

    PubMed  CAS  Google Scholar 

  10. Hata K, Whittaker P, Kloner RA, Przyklenk K (1999) Brief myocardial ischemia attenuates platelet thrombosis in remote, damaged, and stenotic carotid arteries. Circulation 100:843–848

    PubMed  CAS  Google Scholar 

  11. Przyklenk K, Hata K, Whittaker P, Elliott GT (2000) Monophosphoryl lipid A: a novel nitric oxide-mediated therapy to attenuate platelet thrombosis? J Cardiovasc Pharmacol 35:366–375

    Article  PubMed  CAS  Google Scholar 

  12. Wu D, Vanhoorelbeke K, Cauwenberghs N, Meiring M, Depraetere H, Kotze HF, Deckmyn H (2002) Inhibition of the von Willebrand (VWF)–collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons. Blood 99:3623–3628

    Article  PubMed  CAS  Google Scholar 

  13. Matsuno H, Uematsu T, Nagashima S, Nakashima M (1991) Photochemically induced thrombosis model in rat femoral artery and evaluation of effects of heparin and tissue-type plasminogen activator with use of this model. J Pharmacol Methods 25:303–317

    Article  PubMed  CAS  Google Scholar 

  14. Fukuchi M, Uematsu T, Araki S, Nakashima M (1992) Photochemically induced thrombosis of the rat coronary artery and functional evaluation of thrombus formation by occurrence of ventricular arrhythmias. Effects of acetylsalicylic acid and a thromboxane A2 synthetase inhibitor of thrombus formation. Naunyn-Schmiedeberg’s Arch Pharmacol 346:550–554

    Article  CAS  Google Scholar 

  15. Eitzman DT, Westrick RJ, Nabel EG, Ginsburg D (2000) Plasminogen activator inhibitor-1 and vitronectin promote vascular thrombosis in mice. Blood 95:577–580

    PubMed  CAS  Google Scholar 

  16. Danenberg HD, Szalai AJ, Swaminathan RV, Peng L, Chen Z, Seifert P, Fay WP, Simon DI, Edelman ER (2003) Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice. Circulation 108:512–515

    Article  PubMed  CAS  Google Scholar 

  17. Nieman MT, Warnock M, Hasan AA, Mahdi F, Lucchesi BR, Brown NJ, Murphey LJ, Schmaier AH (2004) The preparation and characterization of novel peptide antagonists to thrombin and factor VIIa and activation of protease-activated receptor 1. J Pharmacol Exp Ther 311:492–501

    Article  PubMed  CAS  Google Scholar 

  18. Bodary PF, Vargas FB, King SA, Jongeward KL, Wickenheiser KJ, Eitzman DT (2005) Pioglitazone protects against thrombosis in a mouse model of obesity and insulin resistance. J Thromb Haemost 3:2149–2153

    Article  PubMed  CAS  Google Scholar 

  19. Bodary PF, Gu S, Shen Y, Hasty AH, Buckler JM, Eitzman DT (2005) Recombinant leptin promotes atherosclerosis and thrombosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 25:1634

    CAS  Google Scholar 

  20. Furukoji E, Matsumoto M, Yamashita A, Yagi H, Sakurai Y, Marutsuka K, Hatakeyama K, Morishita K, Fujimura Y, Tamura S, Asada Y (2005) Adenovirus-mediated transfer of human placental ectonucleoside triphosphate diphosphohydrolase to vascular smooth muscle cells suppresses platelet aggregation in vitro and arterial thrombus formation in vivo. Circulation 111:808–815

    Article  PubMed  CAS  Google Scholar 

  21. Angelillo-Scherrer A, Burnier L, Flores N, Savi P, DeMol M, Schaeffer P, Herbert JM, Lemke G, Goff SP, Matsushima GK, Earp HS, Vesin C, Hoylaerts MF, Plaisance S, Collen D, Conway EM, Wehrle-Haller B, Carmeliet P (2005) Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J Clin Invest 115:237–246

    Article  PubMed  CAS  Google Scholar 

  22. Damiano BP, Mitchell JA, Giardino E, Corcoran T, Haertlein BJ, de Garavilla L, Kauffman JA, Hoekstra WJ, Maryanoff BE, Andrade-Gordon P (2001) Antiplatelet and antithrombotic activity of RWJ-53308, a novel orally active glycoprotein IIb/IIIa antagonist. Thromb Res 104:113–126

    Article  PubMed  CAS  Google Scholar 

  23. Fay WP, Parker AC, Ansari MN, Zheng X, Ginsburg D (1999) Vitronectin inhibits the thrombotic response to arterial injury in mice. Blood 93:1825–1830

    PubMed  CAS  Google Scholar 

  24. Kurz KD, Main BW, Sandusky GE (1990) Rat model of arterial thrombosis induced by ferric chloride. Thromb Res 60:269–280

    Article  PubMed  CAS  Google Scholar 

  25. Roux S, Carteaux JP, Hess P, Falivene L, Clozel JP (1994) Experimental carotid thrombosis in the guinea pig. Thromb Haemost 71:252–256

    PubMed  CAS  Google Scholar 

  26. Yokoyama S, Ikeda H, Haramaki N, Yasukawa H, Murohara T, Imaizumi T (2005) Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet–leukocyte aggregates. J Am Coll Cardiol 45:1280–1286

    Article  PubMed  CAS  Google Scholar 

  27. Butler KD, Ambler J, Dolan S, Giddings J, Talbot MD, Wallis RB (1992) A non-occlusive model of arterial thrombus formation in the rat and its modification by inhibitors of platelet function, or thrombin activity. Blood Coagul Fibrinolysis 3:155–165

    PubMed  CAS  Google Scholar 

  28. Daykin HJ, Sturgeon SA, Jones C, Wright CE (2006) Arterial antithrombotic effects of aspirin, heparin, enoxaparin and clopidogrel alone, or in combination, in the rat. Thromb Res E-pub ahead of print: Jan 9

  29. Sturgeon SA, Jones C, Angus JA, Wright CE (2006) Adaptation of the Folts and electrolytic methods of arterial thrombosis for the study of anti-thrombotic molecules in small animals. J Pharmacol Toxicol Methods 53:20–29

    Article  PubMed  CAS  Google Scholar 

  30. Schumacher WA, Steinbacher TE, Megill JR, Durham SK (1996) A ferret model of electrical-induction of arterial thrombosis that is sensitive to aspirin. J Pharmacol Toxicol Methods 35:3–10

    Article  PubMed  CAS  Google Scholar 

  31. de Lima Santos H, Fortes Rigos C, Claudio Tedesco A, Ciancaglini P (2005) Rose bengal located within liposome do not affect the activity of inside–out oriented Na,K-ATPase. Biochim Biophys Acta 1715:96–103

    Article  PubMed  CAS  Google Scholar 

  32. Vandeplassche G, Bernier M, Thone F, Borgers M, Kusama Y, Hearse DJ (1990) Singlet oxygen and myocardial injury: ultrastructural, cytochemical and electrocardiographic consequences of photoactivation of rose bengal. J Mol Cell Cardiol 22:287–301

    Article  PubMed  CAS  Google Scholar 

  33. Przyklenk K, Whittaker P (2000) Brief antecedent ischemia enhances recombinant tissue plasminogen activator-induced coronary thrombolysis by adenosine-mediated mechanism. Circulation 102:88–95

    PubMed  CAS  Google Scholar 

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Acknowledgement

This study was supported by a grant from the National Institutes of Health, Bethesda, MD (# R01 HL072684).

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Correspondence to Karin Przyklenk.

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Przyklenk, K., Whittaker, P. Adaptation of a photochemical method to initiate recurrent platelet-mediated thrombosis in small animals. Lasers Med Sci 22, 42–45 (2007). https://doi.org/10.1007/s10103-006-0410-1

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