Oxidized LDL, a critical factor in atherogenesis☆

There is a great deal of experimental, epidemiological, and clinical evidence suggesting that disorders of lipid metabolism play an important role in the pathogenesis of atherosclerosis.To date, there have been many studies investigating the mechanisms by which high levels of LDL-cholesterol affect biology of vessels and cause atherosclerotic lesion formation [1,2].It has become abundantly clear over the last decade that the oxidatively modified form of LDL (ox-LDL) is more important than native LDL in atherogenesis.The study in this issue of Cardiovascular Research by Zhu et al. [3] demonstrates that ox-LDL downregulates ATPbinding cassette transporter-1 (ABCA1) in endothelial cells in a dose-dependent manner by inhibiting liver X receptor (LXR) activation.Ox-LDL also attenuates LXR activation by blocking LXR ligand binding and interfering with the generation of 27-hydroxycholesterol, an LXR endogenous ligand.Further, ox-LDL inhibits exogenous cholesterol and oxysterol-induced endothelial ABCA1 induction.Such activity of ox-LDL may contribute to endothelial dysfunction since ABCA1 mediates the active efflux of cholesterol and phospholipids, playing an important role in cholesterol homeostasis and thereby atherogenesis.