Phosphatidylcholine hydroperoxide promotes VEGF-induced angiogenesis in endothelial cells and rat aorta ring cultures

Background: Phosphatidylcholine hydroperoxide (PCOOH) is a primary oxidation product of PC, and is markedly accumulated in blood plasma and arterial walls in atherosclerotic animals and humans. The role of PCOOH in the induction of angiogenesis is unknown. Methods: In this study, we investigated whether PCOOH stimulated angiogenic responses (e.g., vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, and tube formation, and angiogenesis-related gene/protein expression) in human umbilical vein endothelial cells (HUVEC) and in an ex vivo rat aorta model. Results: VEGF induced proliferation, migration, and tube formation of HUVEC, and these angiogenic responses were all enhanced by PCOOH but not by native (nonoxidized) PC. The angiogenic effects of PCOOH are considered to be mediated via generation of reactive oxygen species and activation of both PI3K/AKT and MAPK pathways. The angiogenic activities of PCOOH were also confirmed by the rat aortic ring assay. Conclusions: These results indicate that PCOOH can elicit several angiogenic responses. General significance: The present study implies an important role of PCOOH in atherosclerosis progression and plague instability. (C) 2011 Elsevier B.V. All rights reserved.