Oxysterols in Vascular Cells and Role in Atherosclerosis

TL;DR

This paper reviews how oxysterols, oxidized cholesterol derivatives, contribute to vascular cell dysfunction and the development of atherosclerosis, highlighting their biological effects and potential protective roles of HDL.

Contribution

It provides a comprehensive overview of the role of oxysterols in atherogenesis and their impact on vascular cell functions, emphasizing mechanisms of oxidative stress and inflammation.

Findings

Oxysterols accumulate in atheroma plaques and promote inflammation.

Oxysterols induce oxidative stress and apoptosis in vascular cells.

HDL can facilitate the removal of oxysterols from macrophages.

Abstract

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 display proatherogenic activities through multiple and complex mechanisms which lead to dysfunctions of vascular cells (endothelial cells, smooth muscle cells and macrophages). Oxidized LDL 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 stimulating the efflux of oxysterols that have accumulated in foamy macrophages.