TY - JOUR
T1 - Vascular endothelial growth factor regulation of Weibel-Palade-body exocytosis
AU - Matsushita, Kenji
AU - Yamakuchi, Munekazu
AU - Morrell, Craig N.
AU - Ozaki, Michitaka
AU - O'Rourke, Brian
AU - Irani, Kaikobad
AU - Lowenstein, Charles J.
PY - 2005/1/1
Y1 - 2005/1/1
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2004-04-1519
DO - 10.1182/blood-2004-04-1519
M3 - Article
C2 - 15345585
AN - SCOPUS:11144230481
SN - 0006-4971
VL - 105
SP - 207
EP - 214
JO - Blood
JF - Blood
IS - 1
ER -