ISSN: 1305-385X
Hakkında: Özel sayılar şeklinde yayınlanır.
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The Pathogenesis Of Atherosclerosis
Dr. Zeki ÖNGEN,a Dr. Yeşim YILMAZb
aKardiyoloji AD, İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi,bÖzel Haznedar Sağlık Hastanesi, İSTANBUL
Atherosclerosis is a continuous and dynamic process that primariliy affects the intimal layer of medium and large sized arteries. The basic step of atherosclerosis is endothelial dysfunction, which is known to be related to the atherosclerotic risk factors. The decrease of nitric oxide (NO) secretion and increase of endothelin secretion from endothelial cells, favors vasoconstriction and trombosit aggregation. Circulating low density lipoprotein molecules (LDL) find easy access through the dysfunctioning endothelium and accumulate in the subendothelium. Here, the first oxidation of LDL particles is done by endothelial cells. These minimally modified LDL (mmLDL) particles stimulate MCP-1 secretion which is chemotactic for circulating monocytes; monocytes arriving at the lesion turn in to macrophages. Full oxidation, which involves modification of apo-B100 molecule, occurs in macrophages. Oxidized LDL is chemotactic for monoctes, cytotoxic for endothelial cells and smooth muscle cells; stimulates the production and secretion of some growth factors and cytokines; also stimulates expression of adhesion molecules (VCAM-1, ICAM-1) on endothelial cells. Adhesion molecules help circulating monocytes and T-lymphoctes sticking to the endothellium easily. Oxidized LDL is recognized by the scavanger receptors found on macrophages and smooth muscle cells. Macrophages and to a lesser extent smooth muscle cells, that phagocytize and degrade LDL molecules and store them as cholesteryl esthers are the so called foam cells. Foam cells secrete TNF- and metalloproteinases. As the lesion progresses apoptosis of macrophages occur releasing the intacellular lipid to the extracellular area. Some extracellular lipid also comes directly from circulating LDL. At this time metalloproteinases degrade extracellular matrix proteins. Thus a space filled with cholesterol and cellular degradation products occur in the matrix of intimal layer: this is the lipid core. Growth factors like PDGF and FGF stimulate the migration and proliferation of smooth mucle cells from media to intima. These cells are responsible for the production of matrix proteins and hence the fibrous cap overlying the lipid core. Fibrous cap is a dynamic structure under continuous production and degradation. The vulnerability of the lesion is primarily defined by the thickness of the fibrous cap. In 1995 American Heart Association divided the atherosclerotic lesion into six types and five stages. Stage1 lesions involve Type I to III lesions. Type I and II are fatty streaks made up of lipid laden macrophages. In Type III lesions some extacellular lipid doplets and cell degradation products are found. In Stage 2 atheroma is formed with the coalescence of extracellular lipid into a lipid core, intimal layer is damaged (type IV). Type Va has a thin fibrous cap over lipid core. Stage 3 lesions are ‘complicated’ type VI lesions that formes when erosion or fissuring of Type IV or Va lesions results in thrombus formation. If the thrombus is occlusive, this is a Stage 4 lesion. When the damage is repaired and trombus organized, fibrotic Type Vb and Vc lesions, which are the typical forms of Stage 5, are formed.Keywords: Atherosclerosis, oxidized LDL, endothelial dysfunctionTurkiye Klinikleri J Int Med Sci 2006, 2(7):1-9
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