Oxidized Monocyte-Derived Macrophages in Aortic Atherosclerotic Lesion from Apolipoprotein E-Deficient Mice and from Human Carotid Artery Contain Lipid Peroxides and Oxysterols

oxLDL-induced decrease in lipid order of membrane domains is inversely correlated with endothelial stiffness and network formation

“…Furthermore, two additional lines of evidence support our hypothesis that a decrease in membrane order induces endothelial stiffening. First, we show that exposing the cells to 7-keto-cholesterol, a major oxysterol component of oxLDL (13,28), results in a decrease in lipid order and an increase in cell stiffness. In addition, the same inverse correlation between the two parameters is observed in cells enriched with androstenol, a sterol known to disrupt lipid packing of the domains (47).…”

“…To test further whether oxidation of cholesterol itself may be sufficient to induce the same effects on membrane stiffness as oxLDL particles, cells were exposed to 7-keto-cholesterol, a major oxysterol found in oxLDL (13,28). It has also been shown earlier that incorporation of 7-keto-cholesterol results in a decrease in lipid packing of ordered lipid domains of the liposomes compared with cholesterol (29,46).…”

Atheroprotective Potential of Macrophage-Derived Phospholipid Transfer Protein in Low-Density Lipoprotein Receptor-Deficient Mice Is Overcome by Apolipoprotein AI Overexpression

“…Finally, isolated PLTPϪ/Ϫ macrophages displayed a higher ability to oxidize exogenous LDL oxidation than PLTPϩ/ϩ macrophages. Because oxidative injury to monocytes/macrophages is a key factor in atherogenesis, 27 and ␣-tocopherol participates in the regulation of macrophage oxidative status, 28 abnormal cellular amounts of ␣-tocopherol and oxidative status could also explain the proatherogenic effect of macrophage PLTP deficiency.…”

7-Ketocholesterol, a Major Oxysterol, Promotes Pi-Induced Vascular Calcification in Cultured Smooth Muscle Cells

“…Vascular calcification is a common event in the pathogenesis of arteriosclerosis in dialysis patients and has been positively correlated with an increased risk of myocardial infarction 2) . The development of calcification impairs organizational flexibility advanced atherosclerotic plaqes 6) , especially in foam cells around the necrotic core 7) , and accelerate arterial calcification via the induction of apoptosis on arterial smooth muscle cells (SMC) 8) . 7-ketocholesterol (7kc), a major oxysterol in plaques, induces vascular SMC death with features of apoptosis, such as nuclear condensation and internucleosomal DNA fragmentation 9) , through caspase 3 activation 10) .…”