Abstract 11225: Statin Inhibits Oxidized Phospholipid Povpc- Induced Endothelial to Mesenchymal Transition

IntroductionEndothelial to mesenchymal transition (EndMT) plays an important role in atherosclerosis. POVPC (1-Palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine), an oxidized phospholipid and the oxidation product of oxidized low-density lipoprotein, has been found in atherosclerotic lesions. We and others recently demonstrated that POVPC could impair endothelial function and might promote atherosclerosis. However, the effects of POVPC on EndMT are unclear. Statin has been widely used as an anti- atherosclerosis drug. The effects of statin on POVPC-induced EndMT also remian unknown.HypothesisPOVPC induces EndMT and statin prevent POVPC-induced EndMT.MethodsHuman aortic endothelial cells were treated with POVPC for 48 h with/without pretreated with simvastatin. Endothelial cell morphology were observed. Nitric oxide (NO) production and superoxide anion generation (O2) were measured. The expression of specific endothelial markers cluster of differentiation 31 (CD31) and mesenchymal markers alpha smooth muscle actin (α-SMA) were detected by immunofluorescence and immunoblotting. The expression of transforming growth factor beta (TGF-β) and the expression and phosphorylation of Smad were also determined.ResultsPOVPC induced the cellular morphology transformation from cobblestone-like endothelial cells into spindle-like mesenchymal cells. POVPC decreased NO production and increased O2 generation. POVPC also inhibited expression of CD31, but stimulated the expression of α-SMA and TGF-β as well as the phosphorylation of Smad. Pretreated with simvastatin can prevent these effects of POVPC.ConclusionsPOVPC can induce EndMT and statin can prevent POVPC-induced EndMT. These findings suggest that one of the mechanisms of atherosclerosis may be POVPC-induced EndMT and statin may inhibit atherosclerosis, at least in part, by preventing POVPC-induced EndMT.