Matsushita Kenji, Yamakuchi Munekazu, Morrell Craig N, Ozaki Michitaka, O'Rourke Brian, Irani Kaikobad, Lowenstein Charles J
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Blood. 2005 Jan 1;105(1):207-14. doi: 10.1182/blood-2004-04-1519. Epub 2004 Sep 2.
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-gamma (PLC-gamma) 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.
血管内皮生长因子（VEGF）不仅调节血管生成、血管通透性和血管舒张，还促进血管炎症。然而，VEGF促炎作用的分子基础尚不清楚。我们现在表明，VEGF激活内皮细胞的魏尔-帕拉德小体胞吐作用，释放能够引起血管血栓形成和炎症的血管活性物质。VEGF部分通过钙和磷脂酶C-γ（PLC-γ）信号转导触发内皮细胞胞吐作用。然而，VEGF还通过激活内皮型一氧化氮合酶（eNOS）产生一氧化氮（NO）来调节内皮细胞胞吐作用，NO使N-乙基马来酰亚胺敏感因子（NSF）亚硝基化并抑制胞吐作用。因此，VEGF在调节内皮细胞胞吐作用中起双重作用，触发促进和抑制内皮细胞胞吐作用的途径。内皮细胞胞吐作用的调节可能解释了VEGF促炎作用的部分原因。
