New tricks for old dogs: nonthrombotic effects of thrombin in vessel wall biology.
Thrombin is a serine protease that potently activates platelets and catalyzes the conversion of fibrinogen to fibrin. Thrombin also exerts direct effects on vascular cells, such as smooth muscle cells, via interactions with members of the protease-activated receptor family. Evidence in several animal models implicates thrombin-mediated signaling events in the response to injury that typifies vascular lesion formation in atherosclerosis and restenosis. In this review, we examine the activation of protease-activated receptors by thrombin, the downstream signaling events mediated by these receptors, and the physiological role of thrombin in vascular cells and vascular disease.
Patterson
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Program in Molecular Cardiology and Department of Medicine, Lineberger Comprehensive Cancer Center and Center for Thrombosis, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7075, USA. cpatters@med.unc.edu
Stouffer
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GA
Madamanchi
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N
Runge
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MS
D000818:Animals; D017209:Apoptosis; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D017395:Plasminogen Activator Inhibitor 1; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D013917:Thrombin