52 HIGH-DENSITY LIPOPROTEIN MODULATES OXIDIZED PHOSPHOLIPID SIGNALING IN ENDOTHELIAL CELLS FROM PROINFLAMMATORY TO ANTI-INFLAMMATORY. Issue 1 (1st January 2007)

• Record Type: Journal Article
• Authors: Gharavi, N. M.; Gargalovic, P. S.; Chang, I.; Araujo, J.; Watson, A. D.; Lusis, A. J.; Berliner, J. A.
• Is Part Of: Journal of investigative medicine. Volume 55:Issue 1(2007)
• Page Start: S84
• Page End: S84
• Publication Date: 2007-01-01
• Subjects: Clinical medicine -- Periodicals; Medicine -- Research -- Periodicals; Medicine; Research -- United States; Clinical medicine; Medicine -- Research; Periodicals; 616.075
• Languages: English
• ISSNs: 1081-5589

Abstract

Abstract : 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 (EC) to induce a complex inflammatory response. Previously, we demonstrated induction of genes regulating chemotaxis, sterol biosynthesis, the unfolded protein response, and redox homeostasis by Ox-PAPC in human aortic EC (HAEC). Activation of the c-Src kinase/STAT3 pathway and the endothelial nitric oxide synthase (eNOS)/sterol regulatory element binding protein (SREBP) pathway were shown to regulate several of these inflammatory effects of Ox-PAPC in HAEC. High-density lipoprotein (HDL) has anti-inflammatory and antioxidant properties. The goal of the current studies was to determine the role of HDL in regulating Ox-PAPC signaling in HAEC. Using quantitative real-time PCR and Western analysis, we demonstrated that pretreatment of HAEC with HDL for 1 hour, followed by cotreatment, reduced the induction of chemotactic, sterol biosynthetic and UPR genes, by Ox-PAPC and PEIPC. Furthermore, treatment with HDL inhibited the activation of c-Src kinase, STAT3, and SREBP and reversed the uncoupling of eNOS triggered by Ox-PAPC. Finally, we demonstrated that treatment with HDL did not inhibit Ox-PAPC and PEIPC activation of redox pathways, which protect the cell from the effects of oxidative stress. Taken together, these studies demonstrated that HDL inhibits the proinflammatory effects of Ox-PAPC and PEIPC while maintaining the antioxidant activities of these oxidized lipids.