Abstract
1. The antithrombotic effect of aurintricarboxylic acid (ATA) which inhibits binding of von Willebrand factor (vWF) to platelet glycoprotein lb (GPlb) receptor was evaluated in photochemically-induced thrombosis models in the femoral artery of rats and guinea-pigs. 2. ATA at a dose of 10 mg kg-1 significantly prolonged the time required for thrombotic occlusion of the artery in rats. The antithrombotic efficacy was associated with a significant inhibition of platelet retention and ex vivo botrocetin-induced platelet aggregation. 3. On the other hand, in guinea-pigs, ATA at the same dose inhibited the platelet retention and the platelet aggregation, but did not prevent thromboocclusion. 4. ATA inhibited aggregation of washed platelets from rats or guinea-pigs in response to botrocetin and thrombin in a dose-dependent manner (1-30 microM), and to the same extent. 5. ATA moderately increased activated partial thromboplastin time and bleeding time in both species. 6. These results indicate that vWF may play a role in the development of occlusive arterial thrombosis in the rat, but not in the guinea-pig. 7. The antithrombotic activity of ATA may partly arise from its inhibitory effect on thrombin, in addition to that on the vWF-GPlb pathway
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- Bellinger D. A., Nichols T. C., Read M. S., Reddick R. L., Lamb M. A., Brinkhous K. M., Evatt B. L., Griggs T. R. Prevention of occlusive coronary artery thrombosis by a murine monoclonal antibody to porcine von Willebrand factor. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8100–8104. doi: 10.1073/pnas.84.22.8100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Girma J. P., Fressinaud E., Christophe O., Rouault C., Obert B., Takahashi Y., Meyer D. Aurin tricarboxylic acid inhibits platelet adhesion to collagen by binding to the 509-695 disulphide loop of von Willebrand factor and competing with glycoprotein Ib. Thromb Haemost. 1992 Dec 7;68(6):707–713. [PubMed] [Google Scholar]
- Hirata Y., Takiguchi Y., Wada K., Matsuno H., Umemura K., Uematsu T., Nakashima M. Roles of platelet-activating factor, thromboxane A2, ADP and thrombin in thrombogenesis in the guinea pig. Eur J Pharmacol. 1993 Feb 16;231(3):421–425. doi: 10.1016/0014-2999(93)90119-3. [DOI] [PubMed] [Google Scholar]
- Humphries J. E., Yirinec B. A., Hess C. E. Atherosclerosis and unstable angina in Bernard-Soulier syndrome. Am J Clin Pathol. 1992 May;97(5):652–655. doi: 10.1093/ajcp/97.5.652. [DOI] [PubMed] [Google Scholar]
- Ikeda Y., Handa M., Kawano K., Kamata T., Murata M., Araki Y., Anbo H., Kawai Y., Watanabe K., Itagaki I. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress. J Clin Invest. 1991 Apr;87(4):1234–1240. doi: 10.1172/JCI115124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawasaki T., Kaku S., Kohinata T., Sakai Y., Taniuchi Y., Kawamura K., Yano S., Takenaka T., Fujimura Y. Inhibition by aurintricarboxylic acid of von Willebrand factor binding to platelet GPIb, platelet retention, and thrombus formation in vivo. Am J Hematol. 1994 Sep;47(1):6–15. doi: 10.1002/ajh.2830470103. [DOI] [PubMed] [Google Scholar]
- Kinlough-Rathbone R. L., Packham M. A. Unexpected effects of aurin tricarboxylic acid on human platelets. Thromb Haemost. 1992 Aug 3;68(2):189–193. [PubMed] [Google Scholar]
- Kroll M. H., Harris T. S., Moake J. L., Handin R. I., Schafer A. I. von Willebrand factor binding to platelet GpIb initiates signals for platelet activation. J Clin Invest. 1991 Nov;88(5):1568–1573. doi: 10.1172/JCI115468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsuno H., Uematsu T., Nagashima S., Nakashima M. 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. 1991 Jul;25(4):303–317. doi: 10.1016/0160-5402(91)90030-9. [DOI] [PubMed] [Google Scholar]
- McGhie A. I., McNatt J., Ezov N., Cui K., Mower L. K., Hagay Y., Buja L. M., Garfinkel L. I., Gorecki M., Willerson J. T. Abolition of cyclic flow variations in stenosed, endothelium-injured coronary arteries in nonhuman primates with a peptide fragment (VCL) derived from human plasma von Willebrand factor-glycoprotein Ib binding domain. Circulation. 1994 Dec;90(6):2976–2981. doi: 10.1161/01.cir.90.6.2976. [DOI] [PubMed] [Google Scholar]
- Moake J. L., Turner N. A., Stathopoulos N. A., Nolasco L., Hellums J. D. Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin. Blood. 1988 May;71(5):1366–1374. [PubMed] [Google Scholar]
- Nichols T. C., Bellinger D. A., Johnson T. A., Lamb M. A., Griggs T. R. von Willebrand's disease prevents occlusive thrombosis in stenosed and injured porcine coronary arteries. Circ Res. 1986 Jul;59(1):15–26. doi: 10.1161/01.res.59.1.15. [DOI] [PubMed] [Google Scholar]
- Phillips M. D., Moake J. L., Nolasco L., Turner N. Aurin tricarboxylic acid: a novel inhibitor of the association of von Willebrand factor and platelets. Blood. 1988 Dec;72(6):1898–1903. [PubMed] [Google Scholar]
- Ruggeri Z. M., Zimmerman T. S. von Willebrand factor and von Willebrand disease. Blood. 1987 Oct;70(4):895–904. [PubMed] [Google Scholar]
- Sakariassen K. S., Nievelstein P. F., Coller B. S., Sixma J. J. The role of platelet membrane glycoproteins Ib and IIb-IIIa in platelet adherence to human artery subendothelium. Br J Haematol. 1986 Aug;63(4):681–691. doi: 10.1111/j.1365-2141.1986.tb07552.x. [DOI] [PubMed] [Google Scholar]
- Saniabadi A. R., Umemura K., Matsumoto N., Sakuma S., Nakashima M. Vessel wall injury and arterial thrombosis induced by a photochemical reaction. Thromb Haemost. 1995 May;73(5):868–872. [PubMed] [Google Scholar]
- Strony J., Phillips M., Brands D., Moake J., Adelman B. Aurintricarboxylic acid in a canine model of coronary artery thrombosis. Circulation. 1990 Mar;81(3):1106–1114. doi: 10.1161/01.cir.81.3.1106. [DOI] [PubMed] [Google Scholar]
- Takiguchi Y., Asai F., Wada K., Hayashi H., Nakashima M. Antithrombotic effect of a novel recombinant hirudin analogue, CX-397, in a rat arterial thrombosis model. Br J Pharmacol. 1995 Dec;116(7):3056–3060. doi: 10.1111/j.1476-5381.1995.tb15963.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takiguchi Y., Asai F., Wada K., Nakashima M. Comparison of antithrombotic effects of GPIIb-IIIa receptor antagonist and TXA2 receptor antagonist in the guinea-pig thrombosis model: possible role of TXA2 in reocclusion after thrombolysis. Thromb Haemost. 1995 Apr;73(4):683–688. [PubMed] [Google Scholar]
- Takiguchi Y., Wada K., Nakashima M. Comparison of the inhibitory effects of the TXA2 receptor antagonist, vapiprost, and other antiplatelet drugs on arterial thrombosis in rats: possible role of TXA2. Thromb Haemost. 1992 Oct 5;68(4):460–463. [PubMed] [Google Scholar]
- Tomita T., Umegaki K., Hayashi E. Basic aggregation properties of washed rat platelets: correlation between aggregation, phospholipid degradation, malondialdehyde, and thromboxane formation. J Pharmacol Methods. 1983 Aug;10(1):31–44. doi: 10.1016/0160-5402(83)90012-8. [DOI] [PubMed] [Google Scholar]
- Yao S. K., Ober J. C., Garfinkel L. I., Hagay Y., Ezov N., Ferguson J. J., Anderson H. V., Panet A., Gorecki M., Buja L. M. Blockade of platelet membrane glycoprotein Ib receptors delays intracoronary thrombogenesis, enhances thrombolysis, and delays coronary artery reocclusion in dogs. Circulation. 1994 Jun;89(6):2822–2828. doi: 10.1161/01.cir.89.6.2822. [DOI] [PubMed] [Google Scholar]


