Tissue factor in acute coronary syndromes.
Thrombosis at the site of atherosclerotic plaque disruption is the principal cause of acute coronary syndromes. The severity of the clinical consequences is determined by the extent and the progression of the thrombus that are caused by local and systemic factors. In atherosclerotic lesions mediators induce tissue factor (TF) in macrophages, smooth muscle cells, and endothelial cells. Procoagulant microparticles in the lipid core further enhance the thrombogenicity of the plaque. In addition, in acute coronary syndromes circulating monocytes and microparticles express TF and, thereby, contribute to systemic procoagulant activity. As a regulatory mechanism surface-bound, endogenous tissue factor pathway inhibitor-1 (TFPI) inhibits TF activity by translocation of the quaternary complex TF-FVIIa-FXa-TFPI into glycosphingolipid-rich microdomains more efficiently than exogenously added TFPI. This inhibition occurs not only in endothelial cells but also on circulating monocytes and presumably microparticles. Because therapeutic thrombolysis in acute myocardial infarction degrades TFPI, a prothrombotic state due to unopposed TF activity may occur. Several studies have demonstrated a contribution of local and bloodborne TF to thrombus formation; a direct relationship with the clinical outcome, however, awaits further studies. This article discusses the current understanding of the role of TF and its regulation by TFPI in acute coronary syndromes.
Ott
Ilka
I
Deutsches Herzzentrum und 1 Medizinische Klinik der Technischen Universität Munich, Germany. ott@dhm.mhn.de
D000789:Angina, Unstable / Q000188:drug therapy / Q000503:physiopathology*; D000990:Antithrombin III / Q000502:physiology; D003324:Coronary Artery Disease / Q000503:physiopathology; D003328:Coronary Thrombosis / Q000503:physiopathology; D006801:Humans; D008074:Lipoproteins / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000502:physiology*
D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D000990:Antithrombin III; D013925:Thromboplastin