High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1

• DOI: 10.1073/pnas.0704602104
• Publication Date: 2007-09-11T01:05:07Z
• Authors: Naoki Terasaka; Nan Wang; Laurent Yvan-Charvet; Alan R. Tall
• Keywords: ABCG1; Oxysterol; Efflux; Reverse cholesterol transport; Low-density lipoprotein

Oxidized sterols consumed in the diet or formed on low-density lipoprotein (LDL) are toxic to endothelial cells and macrophages thought have a central role promoting atherogenesis. The ATP-binding cassette transporter ABCG1 was recently shown promote efflux of cholesterol from high-denisty (HDL). We show that HDL protects apoptosis induced by loading with free oxidized LDL. protective effect reduced Abcg1(-/-) macrophages, especially after Similarly, exerted against 7-ketocholesterol, major oxysterol present LDL atherosclerotic lesions, Abcg1(+/+), but not macrophages. In transfected 293 cells, 7-ketocholesterol related oxysterols completely dependent expression presence media. contrast, ABCA1 apoA-1 did stimulate into stimulated mice fed high-cholesterol diet, plasma levels were reduced, whereas their accumulated 7-ketocholesterol. These findings indicate specific for onto protecting these oxysterol-induced cytotoxicity.