Lipoproteins, Macrophages and Atherosclerosis
The fatty streak, the earliest recognized gross lesion in the atherogenic process, is characterized by an accumulation of lipid-laden “foam cells”. Recent studies have established that this lesion can -- and usually does -- develop beneath an intact endothelium. Furthermore, it has been shown that most of these cells are derived from circulating monocytes that enter the arterial wall and take up residence there as tissue macrophages. Some of these cells are derived from medial smooth muscle cells, particularly in later lesions, but the majority are macrophages. Early attempts to convert macrophages to foam cells by incubation in the presence of high concentrations of LDL were unsuccessful and this was traced to the rather low number of receptors for native LDL they express. Studies by Goldstein, Brown and coworkers established that the macrophage expresses a unique receptor that can take up chemically acetylated LDL at a sufficiently high rate to generate foam cells in culture. However, there was no evidence that chemical acetylation occurs to any significant extent in vivo. Thus, there remained an unresolved paradox regarding the mechanism of foam cell formation and thus the initiation of the fatty streak.
KeywordsCholesterol Hydrolysis Migration Toxicity Foam
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