Vascular endothelial growth factor receptor 2 plays a role in the activation of aortic endothelial cells by oxidized phospholipids

Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):332-8. doi: 10.1161/01.ATV.0000252842.57585.df. Epub 2006 Nov 16.

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.

Methods and 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cells, Cultured
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology*
  • Enzyme Activation / drug effects
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / physiology
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / physiology
  • Phosphatidylcholines / pharmacology*
  • Phosphorylation / drug effects
  • RNA, Small Interfering / pharmacology
  • Receptors, LDL / genetics
  • Receptors, LDL / physiology
  • Sterol Regulatory Element Binding Proteins / genetics
  • Sterol Regulatory Element Binding Proteins / physiology
  • Thromboplastin / genetics
  • Thromboplastin / physiology
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology
  • Vascular Endothelial Growth Factor Receptor-2 / physiology*

Substances

  • Interleukin-8
  • Phosphatidylcholines
  • RNA, Small Interfering
  • Receptors, LDL
  • Sterol Regulatory Element Binding Proteins
  • oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine
  • Thromboplastin
  • Vascular Endothelial Growth Factor Receptor-2
  • Mitogen-Activated Protein Kinase 3