Atherothrombosis: plaque instability and thrombogenesis.
Hemostasis involves a carefully regulated balance between circulating and endothelium-derived prothrombotic and antithrombotic factors. The unstable or vulnerable plaque facilitates thrombosis, clinically manifest as an acute coronary syndrome (ACS), by creating an environment that favors thrombus formation over prevention of lysis. Endothelial cell dysfunction is integral to both the development of the atherosclerotic lesion as well as its destabilization. The transformation of a stable plaque to an unstable one involves complex interactions among T lymphocytes, macrophages, endothelial cells, and smooth muscle cells. Degradation of the fibrous cap of the atherosclerotic lesion as well as the overexpression of prothrombotic and underexpression of antithrombotic factors by cells within the plaque precede thrombus formation. Accordingly, pharmacological interventions for the treatment of ACS are directed against the initiation and propagation of thrombosis, as well as toward improvement of endothelial function.
Ruberg
Frederick L
FL
Evans Department of Medicine, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118-2526, USA.
Leopold
Jane A
JA
Loscalzo
Joseph
J
D003324:Coronary Artery Disease / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D003328:Coronary Thrombosis / Q000097:blood / Q000209:etiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D012422:Rupture, Spontaneous / Q000209:etiology
D008565:Membrane Proteins