title: Acute and persistent platelet and coagulant activities in atherothrombosis.
abstract: The potential relevance of murine atherothrombosis models for understanding human disease has been debated in the past. Despite this, in the last decade, many thrombosis studies with atherogenic Apoe(-/-) mice have been performed, which provide novel insight into the molecular mechanisms by which platelet and coagulation processes accomplish acute thrombus formation after plaque disruption in vivo. Support for these mechanisms has come from whole blood flow perfusion studies over plaque material in vitro, which are also reviewed in this study. The main plaque-derived triggers for thrombus formation appear to be collagen and tissue factor, next to bioactive mediators such as prostaglandin E2. The atherothrombotic process relies on collagen- and ADP-receptor-induced platelet activation as well as on thrombin/fibrin generation via the extrinsic and intrinsic coagulation pathways. Less is known of the persistent effects of a thrombus on atherosclerosis progression, but evidence suggests roles herein of activated platelets and ongoing thrombin generation.
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
authors.forename: T G
authors.initials: TG
authors.lastname: Mastenbroek
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
authors.forename: J P
authors.initials: JP
authors.lastname: van Geffen
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
authors.forename: J W M
authors.initials: JW
authors.lastname: Heemskerk
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
authors.forename: J M E M
authors.initials: JM
authors.lastname: Cosemans
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics / Q000473:pathology; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005342:Fibrinolysis; D006801:Humans; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D015539:Platelet Activation; D012422:Rupture, Spontaneous; D015398:Signal Transduction; D013927:Thrombosis / Q000097:blood* / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D017395:Plasminogen Activator Inhibitor 1; D003094:Collagen
keywords: atherosclerotic plaque; blood coagulation; mouse; platelets; rupture; thrombosis