High-Density Lipoprotein Modulates Oxidized Phospholipid Signaling in Human Endothelial Cells From Proinflammatory to Anti-inflammatory

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Abstract
Objective— Oxidized 1-palmitoyl-2-arachidonyl-sn-3-glycero-phosphorylcholine (Ox-PAPC) and its component phospholipid, 1-palmitoyl-2-(5,6 epoxyisoprostanoyl)-sn-glycero-3-phosphocholine (PEIPC), which are present in atherosclerotic lesions, activate endothelial cells to induce a complex inflammatory and pro-oxidant response. Previously, we demonstrated induction of genes regulating chemotaxis, sterol biosynthesis, the unfolded protein response, and redox homeostasis by Ox-PAPC in human aortic endothelial cells (HAECs). Activation of the c-Src kinase/signal transducer and activator of transcription 3 and the endothelial nitric oxide synthase/sterol regulatory element binding protein (SREBP) pathways were shown to regulate several of these inflammatory effects of Ox-PAPC in HAECs. The goal of the current studies was to determine the role of high-density lipoprotein (HDL) in regulating Ox-PAPC signaling in HAECs. Methods and Results— Using quantitative real-time polymerase chain reaction, Western analysis, a... Previously, we demonstrated that oxidized 1-palmitoyl-2-arachidonyl-sn-3-glycero-phosphorylcholine and component lipids caused induction of genes regulating chemotaxis, sterol biosynthesis, the unfolded protein response, and redox homeostasis in human aortic endothelial cells. Taken together, these studies demonstrated that high-density lipoprotein inhibits the pro-inflammatory effects of oxidized 1-palmitoyl-2-arachidonyl-sn-3-glycero-phosphorylcholine and phospholipid, 1-palmitoyl-2-(5,6 epoxyisoprostanoyl)-sn-glycero-3-phosphocholine, while maintaining the antioxidant activities of these lipids.