Published online before print September 14, 2006, doi: 10.1161/01.RES.0000245485.04489.ee
© 2006 American Heart Association, Inc.
Integrative Physiology |
Oxidized Phospholipids Stimulate Angiogenesis Via Autocrine Mechanisms, Implicating a Novel Role for Lipid Oxidation in the Evolution of Atherosclerotic Lesions
From the Department of Vascular Biology and Thrombosis Research (V.N.B., O.O., A.K., A.F., E.K., T.A., J.B., D.M., B.R.B., N.L.), Medical University of Vienna, Austria; Department of Research (M.P., T.R.), Basel University Hospital, Switzerland; Division of Cardiology (P.E.), Kantonsspital Luzern, Switzerland; Palladin Institute of Biochemistry (A.M.), Kiev, Ukraine; Departments of Internal Medicine II (P.H., K.R., J.W.) and Dermatology (F.G.), Medical University of Vienna, Austria; Department of Pharmacology; the Cardiovascular Research Center (N.L., A.K.), University of Virginia, Charlottesville, Va; and Novartis Institutes for BioMedical Research (D.M.), Vienna, Austria.
Correspondence to Valery Bochkov, PhD, Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria. E-mail valery.bochkov{at}meduniwien.ac.at
Angiogenesis is a common feature observed in advanced atherosclerotic lesions. We hypothesized that oxidized phospholipids (OxPLs), which accumulate in atherosclerotic vessels can stimulate angiogenesis. We found that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) stimulated the formation of sprouts from endothelial cell spheroids and promoted growth of capillaries into Matrigel plugs in mice. OxPLs stimulated expression of vascular endothelial growth factor (VEGF) in vivo and in several normal and tumor cell types in vitro. In addition, OxPAPC upregulated cyclooxygenase (COX)-2 and interleukin (IL)-8. COX-2 inhibitors, as well as blocking antibodies to IL-8 suppressed activation of sprouting by OxPAPC. We conclude that OxPAPC stimulates angiogenesis via autocrine mechanisms involving VEGF, IL-8, and COX-2–generated prostanoids. Our data suggest that accumulation of OxPLs may contribute to increased growth of blood capillaries in advanced lesions, thus leading to progression and destabilization of atherosclerotic plaques.
Key Words: oxidized phospholipids • atherosclerosis • angiogenesis • plaque destabilization
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