Nonoxidative modifications of lipoproteins in atherogenesis

The key initiating event in atherosclerosis is the retention of plasma Lipo proteins in the subendothelial matrix. Subsequently, a series of biological responses to this retained material leads to specific molecular and cellul ar processes that promote lesion formation. There is considerable evidence that many of these biological responses, notably macrophage cholesteryl est er loading (foam cell formation), require subendothelial modification of th e retained lipoproteins. Oxidation of lipoproteins is one such modification that likely occurs in vivo and promotes certain atherogenic events, but ox idation cannot explain all aspects of atherogenesis, including certain elem ents of macrophage foam cell formation. For this reason, there has been ren ewed 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 com plex formation, and conversion to cholesterol-rich liposomes. The focus is on the evidence that these modifications occur in atherosclerotic lesions a nd on the potential role of these modified lipoproteins in atherogenesis, w ith an emphasis on macrophage foam cell formation.