title: Oxidized phospholipids stimulate angiogenesis via autocrine mechanisms, implicating a novel role for lipid oxidation in the evolution of atherosclerotic lesions.
abstract: 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.
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria. valery.bochkov@meduniwien.ac.at
authors.forename: Valery N
authors.initials: VN
authors.lastname: Bochkov
authors.forename: Maria
authors.initials: M
authors.lastname: Philippova
authors.forename: Olga
authors.initials: O
authors.lastname: Oskolkova
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kadl
authors.forename: Alexander
authors.initials: A
authors.lastname: Furnkranz
authors.forename: Erduan
authors.initials: E
authors.lastname: Karabeg
authors.forename: Taras
authors.initials: T
authors.lastname: Afonyushkin
authors.forename: Florian
authors.initials: F
authors.lastname: Gruber
authors.forename: Johannes
authors.initials: J
authors.lastname: Breuss
authors.forename: Alexander
authors.initials: A
authors.lastname: Minchenko
authors.forename: Diana
authors.initials: D
authors.lastname: Mechtcheriakova
authors.forename: Philipp
authors.initials: P
authors.lastname: Hohensinner
authors.forename: Kathrin
authors.initials: K
authors.lastname: Rychli
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Therese
authors.initials: T
authors.lastname: Resink
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
authors.forename: Bernd R
authors.initials: BR
authors.lastname: Binder
authors.forename: Norbert
authors.initials: N
authors.lastname: Leitinger
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis; D000071097:ADAMTS1 Protein; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology*; D019898:Autocrine Communication; D002465:Cell Movement; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016209:Interleukin-8 / Q000096:biosynthesis; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000209:etiology*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D043925:Angiogenesis Inducing Agents; D016209:Interleukin-8; D010743:Phospholipids; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C486323:Adamts1 protein, mouse