Nonoxidative modifications of lipoproteins in atherogenesis.
The key initiating event in atherosclerosis is the retention of plasma lipoproteins in the subendothelial matrix. Subsequently, a series of biological responses to this retained material leads to specific molecular and cellular processes that promote lesion formation. There is considerable evidence that many of these biological responses, notably macrophage cholesteryl ester loading (foam cell formation), require subendothelial modification of the retained lipoproteins. Oxidation of lipoproteins is one such modification that likely occurs in vivo and promotes certain atherogenic events, but oxidation cannot explain all aspects of atherogenesis, including certain elements of macrophage foam cell formation. For this reason, there has been renewed interest in other modifications of lipoproteins that may be important in atherogenesis. This review addresses five such lipoprotein modifications, namely aggregation, glycation, immune complex formation, proteoglycan complex formation, and conversion to cholesterol-rich liposomes. The focus is on the evidence that these modifications occur in atherosclerotic lesions and on the potential role of these modified lipoproteins in atherogenesis, with an emphasis on macrophage foam cell formation.
Tabas
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Department of Medicine and Anatomy, Columbia University, New York, New York 10032, USA. iat1@columbia.edu
D000936:Antigen-Antibody Complex; D001161:Arteriosclerosis / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D006031:Glycosylation; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry; D008081:Liposomes; D011509:Proteoglycans
D000936:Antigen-Antibody Complex; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008081:Liposomes; D011509:Proteoglycans; D002784:Cholesterol