Inflammation and atherothrombosis.
An immune and inflammatory response involving endothelial and smooth muscle cells accompanies the accumulation of lipids and fibrous materials in atheromatous arteries. The inflammatory response involves not only the intrinsic cells of the artery wall, but also circulating leukocytes. Lymphocytes as well as macrophages participate importantly in this disease process. Plaque composition and vulnerability have emerged as more critical determinants of plaque rupture than the degree of lumenal stenosis. Thus, plaque biology has proven more important than gross morphology in determining the clinical consequences of the disease. Rupture of the atherosclerotic plaque, its thrombotic complications, and their sequelae have gained increased recognition as the proximate causes of disability and death due to related syndromes such as acute myocardial infarction. Arterial thromboses occur much more readily in arteries damaged or distorted by the atherosclerotic process. The consequences of a given plaque disruption and subsequent thrombus formation will depend on both "systemic" or fluid phase determinants and local "solid state" factors. The complex heterogeneous structure of thrombi includes fibrin, platelets, erythrocytes, and leukocytes. The local balance of proteases and inhibitors on the fibrin and cell surfaces will determine thrombus stability and persistence. Enhanced understanding of the processes involved in the development and progression of atherosclerosis and its complications will surely provide areas that can be targeted in the treatment of the disease.
Robbie
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Leducq Center for Cardiovascular Research, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Libby
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D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*