Oxysterols in Vascular Cells and Role in Atherosclerosis

Atherosclerosis is a major cardiovascular complication of diseases associated with elevated oxidative stress such as type 2 diabetes and metabolic syndrome. In these situations, low-density lipoproteins (LDL) undergo oxidation. Oxidized LDL displays proatherogenic activities through multiple and complex mechanisms which lead to dysfunctions of vascular cells (endothelial cells, smooth muscle cells, and macrophages). Oxidized LDLs are enriched in oxidized products of cholesterol called oxysterols formed either by autoxidation, enzymatically, or by both mechanisms. Several oxysterols have been shown to accumulate in atheroma plaques and to play a key role in atherogenesis. Depending on the type of oxysterols, various biological effects are exerted on vascular cells to regulate the formation of macrophage foam cells, endothelial integrity, adhesion and transmigration of monocytes, plaque progression, and instability. Most of these effects are linked to the ability of oxysterols to induce cellular oxidative stress and cytotoxicity mainly through apoptosis and proinflammatory mediators. Like for excess cholesterol, high-density lipoproteins (HDL) can exert antiatherogenic activity by stimulating the efflux of oxysterols that have accumulated in foamy macrophages.