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Atherosclerosis and Thrombus Formation
Oxidation of LDL-Cholesterol
 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.
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Stroke Education
