It is clear that the accumulation of lipids in macrophages and smooth-muscle cells is a central aspect of atherogenesis [Hajjar DP and Nicholson AC, 1995. Ip JH, et al, 1994. DeGraba TJ, et al, 1991]. The interaction between lipids and cellular contributions to atherogenesis has been widely investigated.
In the late 1970s, Brown and Goldstein showed that the hepatic receptor for the low-density-lipoprotein (LDL) particle removes cholesterol from the bloodstream; however, this receptor was not found to play a role in the accumulation of lipids within the foam cells of atherosclerotic lesions. Subsequently, the two investigators demonstrated that another type of LDL receptor, called the “scavenger receptor,” was present on macrophages [Brown MS, Goldstein JL. Science. 1986;232:34]. Later work by Steinberg and colleagues showed that whereas normal LDL is not readily taken up by the scavenger receptor, this receptor does recognize oxidized LDL particles [Steinberg D, et al. N Engl J Med. 1989;320:915].
Oxidation of LDL-cholesterol is induced by free radicals produced by macrophages, endothelial cells, or smooth-muscle cells [DeGraba TJ, et al, 1991]. In addition to its participation in the formation of foam cells, oxidized LDL-cholesterol appears to contribute to atherogenesis in three other ways: (1) It has cytotoxic properties that may promote endothelial injury; (2) it acts as a chemoattractant for circulating monocytes, leading to their increased accumulation with plaques; and (3) oxidized LDL-cholesterol inhibits egress of macrophages from plaques.
Acute Ischemic Stroke: New Concepts of Care
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