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J Thromb Haemost. 2012 Jul;10(7):1207-16. doi: 10.1111/j.1538-7836.2012.04782.x.

The impact of blood coagulability on atherosclerosis and cardiovascular disease.

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  • 1Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands. rinske.loeffen@maastrichtuniversity.nl

Abstract

Although the link between blood coagulation and atherogenesis has been long postulated, only recently, and through the extensive work on transgenic mice, crossbred on an atherogenic background, has the direction of this interaction become visible. In general, hypercoagulability in mice tends to increase atherosclerosis, whereas hypocoagulability reduces the atherosclerotic burden, depending on the mouse model used. The information on a direct relationship between coagulation and atherosclerosis in humans, however, is not that clear. Almost all coagulation proteins, including tissue factor, are found in atherosclerotic lesions in humans. In addition to producing local fibrin, a matrix for cell growth, serine proteases such as thrombin may be very important in cell signaling processes, acting through the activation of protease-activated receptors (PARs). Activation of PARs on vascular cells drives many complex processes involved in the development and progression of atherosclerosis, including inflammation, angiogenesis, and cell proliferation. Although current imaging techniques do not allow for a detailed analysis of atherosclerotic lesion phenotype, hypercoagulability, defined either by gene defects of coagulation proteins or elevated levels of circulating markers of activated coagulation, has been linked to atherosclerosis-related ischemic arterial disease. New, high-resolution imaging techniques and sensitive markers of activated coagulation are needed in order to study a causal contribution of hypercoagulability to the pathophysiology of atherosclerosis. Novel selective inhibitors of coagulation enzymes potentially have vascular effects, including inhibition of atherogenesis through attenuation of inflammatory pathways. Therefore, we propose that studying the long-term vascular side effects of this novel class of oral anticoagulants should become a clinical research priority.

© 2012 International Society on Thrombosis and Haemostasis.

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PMID:
22578148
[PubMed - indexed for MEDLINE]
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