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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden coronary death. Therefore, for event-free survival, the vital question is not why atherosclerosis develops but rather why, after years of indolent growth, it suddenly becomes complicated by life-threatening thrombosis. Therefore, we have to focus on plaque composition and vulnerability to rupture and plaque thrombogenicity rather than on plaque size and stenosis severity. The risk for plaque disruption depends more on plaque vulnerability (plaque type) than on degree of stenosis (plaque size). Lipid-rich and soft plaques are more vulnerable and prone to rupture than collagen-rich and hard plaques. They are also highly thrombogenic after disruption because of high content of tissue factor. There seems to be three major determinants of a plaque's vulnerability to rupture: 1) the size and consistency of the lipid-rich atheromatous core, 2) the thickness of the fibrous cap covering the core, and 3) ongoing inflammation and repair processes within the fibrous cap. Lipid accumulation, cap thinning, lack of smooth muscle cells (smc), and macrophage-related inflammation destabilize plaques, making them vulnerable to rupture. In contrast, smc-related healing and repair processes stabilize plaques, protecting them against disruption. Plaque size or stenosis severity tell nothing about a plaque's vulnerability. Many vulnerable plaques are invisible angiographically due to their small size and compensatory vascular remodeling.
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PMID:Plaque pathology and coronary thrombosis in the pathogenesis of acute coronary syndromes. 1038 96

The past decade has witnessed enormous progress in our understanding of the nature of this process. The development of an atherosclerotic plaque is a complex process which begins with endothelial dysfunction, the trigger for which are factors such as hypercholesterolemia, smoking, hypertension, hyperhomocysteinemia and impaired glucose metabolism. This dysfunction includes increased endothelial permeability to lipoproteins and other plasma constituents, which is mediated by NO, PDGF, prostacyclin, angiotensin II and endothelin; up-regulation of endothelial adhesion molecules including VCAM-1, ICAM-1, and selectins and migration of leukocytes and monocytes-macrophages in the subendothelial space mediated by oxidized LDL, MCP-1, PDGF and MCSF. The next step includes smooth-muscle cells migration (stimulated by PDGF and TGF-beta), T-cell activation (mediated by TNF-alpha and IL-2), formation of foam-cells from macrophages (mediated by oxidized LDL, MCSF, TNF-alpha and IL-1) and platelet adherence and aggregation (stimulated by thromboxane A2, tissue factor etc). The smooth muscle cells form a fibrous cap which confers mechanical stability of the plaque and separates the lipid rich thrombogenic core from the lumen and circulating blood. Whether a plaque will remain intact and therefore stable or rupture and lead to thrombosis causing an acute coronary syndrome (MI, unstable angina pectoris) depends upon a number of factors, the most important of which is its composition. Plaque size plays only a minor role in determining risk of an acute coronary syndrome. Rupture of the fibrous cap occurs due to thinning of the cap caused by an influx and activation of macrophages which release metalloproteinases and other proteolytic enzymes (stimulated by inflammatory cells, particularly T-lymphocytes). These enzymes cause degradation of the fibrous tissue of the cap which can result in thrombous formation and occlusion of the artery. Stable plaques have a thick fibrous cap, a small lipid core, and few inflammatory cells. In contrast, vulnerable plaques have a high lipid content, numerous inflammatory cells, and a thin fibrous cap with reduced collagen and vascular smooth muscle cells in it. Although vulnerable plaques are believed to account for only a small number of all coronary atheromas, they are responsible for most acute coronary events.
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PMID:[New information on the pathophysiology of atherosclerosis]. 1137 94

Immune cells play an important role in atheromatous plaque formation and progression and in the phase of "active plaque" and of the consequent clinical manifestations. Endothelial dysfunction is the first determinant step in atherogenesis by inducing the alteration of vasodilating and antithrombotic properties of the endothelium and of its permeability to lipoproteins. Circulating monocytes are recruited and internalized and lipoproteins are stored in the subendothelial area where they undergo oxidation (oxidized LDL) and are removed by macrophages by means of non-autoregulated scavenger receptors (foam cells). Foam cells are able to express surface receptors and to produce soluble mediators (interleukin-1, tumor necrosis factor-alpha, monocyte chemotactic protein 1) which attract other monocytes, activate endothelial cells and smooth muscle cells. Lymphocytes too are present in these first stages of atherogenesis. If the injurious agents are not removed or nullified by the inflammatory response and the inflammation progresses, the response changes from a protective to an injurious response. Recruitment of monocytes and lymphocytes occurs as a result of the up-regulation of adhesion molecules on both the endothelium and the leukocytes and the plaque progresses to an advanced lesion. Finally the activation of monocytes and T cells induces the plaque activation and rupture in presence of inducing agents such as oxidized LDL. CD4 lymphocytes are common components of atheroma and are mainly localized at the sites of rupture in strict contact with macrophages and smooth muscle cells which express activation surface molecules and which are able to process and to present the antigen to T cells. Activated lymphocytes produce proinflammatory cytokines as interferon-gamma which is able to amplify the inflammatory response but also interleukin-10 which seems to possess a regulatory effect. Activated macrophages release metalloproteinases and other proteolytic enzymes which cause degradation of the matrix, thinning of fibrous cap and plaque destabilization. Both T cells and macrophages produce cytotoxic factors which contribute to the apoptosis. The process may be potentiated by the activation of platelets, tissue factor, coagulation-fibrinolytic system which can contribute to thrombus formation, plaque rupture and artery occlusion.
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PMID:[Immune factors in atherosclerosis]. 1605 40