Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis

Kenji Matsushita, Munekazu Yamakuchi, Craig N. Morrell, Michitaka Ozaki, Brian O'Rourke, Kaikobad Irani, Charles J. Lowenstein

Research output: Contribution to journalArticle

Abstract

Vascular endothelial growth factor (VEGF) not only regulates angiogenesis, vascular permeability, and vasodilation but also promotes vascular inflammation. However, the molecular basis for the proinflammatory effects of VEGF is not understood. We now show that VEGF activates endothelial cell exocytosis of Weibel-Palade bodies, releasing vasoactive substances capable of causing vascular thrombosis and inflammation. VEGF triggers endothelial exocytosis in part through calcium and phospholipase C-γ (PLC-γ) signal transduction. However, VEGF also modulates endothelial cell exocytosis by activating endothelial nitric oxide synthase (eNOS) production of nitric oxide (NO), which nitrosylates N-ethylmaleimide sensitive factor (NSF) and inhibits exocytosis. Thus, VEGF plays a dual role in regulating endothelial exocytosis, triggering pathways that both promote and inhibit endothelial exocytosis. Regulation of endothelial exocytosis may explain part of the proinflammatory effects of VEGF.

Original languageEnglish (US)
Pages (from-to)207-214
Number of pages8
JournalBlood
Volume105
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Matsushita, K., Yamakuchi, M., Morrell, C. N., Ozaki, M., O'Rourke, B., Irani, K., & Lowenstein, C. J. (2005). Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis. Blood, 105(1), 207-214. https://doi.org/10.1182/blood-2004-04-1519