Oxidized phospholipids stimulate angiogenesis via autocrine mechanisms, implicating a novel role for lipid oxidation in the evolution of atherosclerotic lesions.
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.
Bochkov
Valery N
VN
Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria. valery.bochkov@meduniwien.ac.at
Philippova
Maria
M
Oskolkova
Olga
O
Kadl
Alexandra
A
Furnkranz
Alexander
A
Karabeg
Erduan
E
Afonyushkin
Taras
T
Gruber
Florian
F
Breuss
Johannes
J
Minchenko
Alexander
A
Mechtcheriakova
Diana
D
Hohensinner
Philipp
P
Rychli
Kathrin
K
Wojta
Johann
J
Resink
Therese
T
Erne
Paul
P
Binder
Bernd R
BR
Leitinger
Norbert
N
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
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