USMLE Forums - View Single Post - 1st step in pathogenesis of atherosclerosis caused by hyperlipidemia
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Old 01-01-2010
lee-usmle lee-usmle is offline
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The most acceptable theory of atherosclerosis formation follows this sequence:

1- Endothelial cell injury which can be due to several risk factors but the most important are hypertension, nicotin, immune mechanism and hyperlipidemia.
2- This injury leads to accumilation of plasma derived lipids and proteins leading to intimal thickening (atheroma).
3- This will lead to platelet adhesion to the surface of endothelial cells which leads to microthrombi formation and release of PDGF which attracts monocytes to the area.
4- Attracted monocytes become macrophages that engulf cholestrol (foam cells) and also secrete free radicals which causes oxidation of circulating LDL.
5- Oxidized LDL taken up by macrophages through scavenger receptor and this leads to extreme release of IL1 and TNF which inturn attract even more monocytes and stimulate smooth muscle cell and fibroblast proliferation.
6- Fibroblasts lay down collagen and elastin which aids in forming the mature atherosclerotic plaque.
7- Smooth muscles migrate from the media to the intima and transform into secretory cells producing collagen, elastin, IL1, TNF, PDGF, ..etc and serve as important mediators of the process.
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