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

Fingerprint

Weibel-Palade Bodies
Exocytosis
Vascular Endothelial Growth Factor A
Endothelial cells
Blood Vessels
Endothelial Cells
N-Ethylmaleimide-Sensitive Proteins
Inflammation
Signal transduction
Nitric Oxide Synthase Type III
Capillary Permeability
Type C Phospholipases
Vasodilation
Signal Transduction
Nitric Oxide
Thrombosis
Calcium

ASJC Scopus subject areas

  • Hematology

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

Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis. / Matsushita, Kenji; Yamakuchi, Munekazu; Morrell, Craig N.; Ozaki, Michitaka; O'Rourke, Brian; Irani, Kaikobad; Lowenstein, Charles J.

In: Blood, Vol. 105, No. 1, 01.01.2005, p. 207-214.

Research output: Contribution to journalArticle

Matsushita, K, Yamakuchi, M, Morrell, CN, Ozaki, M, O'Rourke, B, Irani, K & Lowenstein, CJ 2005, 'Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis', Blood, vol. 105, no. 1, pp. 207-214. https://doi.org/10.1182/blood-2004-04-1519
Matsushita K, Yamakuchi M, Morrell CN, Ozaki M, O'Rourke B, Irani K et al. Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis. Blood. 2005 Jan 1;105(1):207-214. https://doi.org/10.1182/blood-2004-04-1519
Matsushita, Kenji ; Yamakuchi, Munekazu ; Morrell, Craig N. ; Ozaki, Michitaka ; O'Rourke, Brian ; Irani, Kaikobad ; Lowenstein, Charles J. / Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis. In: Blood. 2005 ; Vol. 105, No. 1. pp. 207-214.
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