title: Vascular endothelial growth factor receptor 2 plays a role in the activation of aortic endothelial cells by oxidized phospholipids.
abstract: OBJECTIVE
  Previous studies have shown that oxidized products of PAPC (Ox-PAPC) regulate cell transcription of interleukin-8, LDL receptor, and tissue factor. This upregulation takes place in part through the activation of sterol regulatory element-binding protein (SREBP) and Erk 1/2. The present studies identify vascular endothelial growth factor receptor 2 (VEGFR2) as a major regulator in the activation of SREBP and Erk 1/2 in endothelial cells activated by Ox-PAPC.
  
  
  RESULTS
  Ox-PAPC induced the phosphorylation of VEGFR2 at Tyr1175 in human aortic endothelial cells. Inhibitors and siRNA for VEGFR2 decreased the transcription of interleukin-8, LDL receptor, and tissue factor in response to Ox-PAPC and the activation of SREBP and Erk 1/2, which mediate this transcription. We provide evidence that the activation of VEGFR2 is rapid, sustained, and c-Src-dependent.
  
  
  CONCLUSIONS
  These data point to a major role of VEGFR2 in endothelial regulation by oxidized phospholipids which accumulate in atherosclerotic lesions and apoptotic cells.
authors.affiliation: Departments of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Zimman
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Mouillesseaux
authors.forename: Thang
authors.initials: T
authors.lastname: Le
authors.forename: Nima M
authors.initials: NM
authors.lastname: Gharavi
authors.forename: Ann
authors.initials: A
authors.lastname: Ryvkin
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Graeber
authors.forename: Tom T
authors.initials: TT
authors.lastname: Chen
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Watson
authors.forename: Judith A
authors.initials: JA
authors.lastname: Berliner
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000502:physiology; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000502:physiology; D013925:Thromboplastin / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology*
chemical_list: D016209:Interleukin-8; D010713:Phosphatidylcholines; D034741:RNA, Small Interfering; D011973:Receptors, LDL; D051779:Sterol Regulatory Element Binding Proteins; C472349:oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine; D013925:Thromboplastin; D040301:Vascular Endothelial Growth Factor Receptor-2; D048052:Mitogen-Activated Protein Kinase 3