Role of thrombosis in atherosclerosis and its complications.
The endothelium is intact but activated and dysfunctioning during the early phase of atherogenesis. Owing to increased endothelial permeability, many blood-derived components, including hemostatic factors, are present in early as well as advanced atherosclerotic lesions. Insudated fibrin(ogen) and related degradation products and thrombin could contribute to atherogenesis by their chemotactic (attracting monocytes/macrophages) and mitogenic (stimulating cell proliferation) properties. All key cells in plaque may express thrombin receptors, indicating that thrombin may play a role in the genesis of uncomplicated atherosclerosis by mediating inflammatory and proliferative processes. Later, endothelial denudation with platelet adherence occurs over mature plaques. Then, incorporation of microthrombi and probably platelet/thrombus-derived growth factors are critical for the progressive growth of the smooth muscle cell-related plaque component. Besides transendothelial influx and incorporation of mural thrombi, blood products in atherosclerotic plaques may originate from hemorrhage through a ruptured plaque surface or from fragile newly formed vessels (neovascularization) frequently found at the base of advanced plaques. Rupture-related plaque progression due to luminal thrombosis and/or plaque hemorrhage is the most important mechanism underlying the unpredictable rapid progression of coronary lesions responsible for acute coronary syndromes. Both platelets and fibrin play a role in the dynamic thrombotic response to plaque rupture.(ABSTRACT TRUNCATED AT 250 WORDS)
Falk
E
E
University Institute of Forensic Medicine, Odense, Denmark.
Fernández-Ortiz
A
A
D000818:Animals; D003324:Coronary Artery Disease / Q000150:complications / Q000209:etiology* / Q000473:pathology; D003328:Coronary Thrombosis / Q000150:complications* / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D012422:Rupture, Spontaneous