Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium
Nitric oxide mediates mitogenic effect of VEGF on coronary venular endothelium
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DOI：
10.1152/ajpheart.1996.270.1.h411
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发表时间：
1996-01-01
影响因子：
4.8
通讯作者：
Ziche, M
中科院分区：
文献类型：
--
作者：
Morbidelli, L;Chang, CH;Ziche, M
血管内皮生长因子（VEGF）是一种分泌性蛋白质，是内皮细胞的特异性生长因子。我们最近已经证明，一氧化氮（NO）的捐助者和血管活性肽促进NO介导的血管舒张诱导血管生成在体内以及内皮细胞的生长和运动在体外，相反，抑制剂NO合成酶抑制血管生成。在这项研究中，我们研究了一氧化氮介导的血管内皮生长因子对培养的微血管内皮细胞的有丝分裂的作用，从冠状动脉毛细血管后微静脉分离。VEGF诱导细胞增殖和DNA合成的剂量依赖性增加。NO的作用通过监测在存在和不存在NO合酶阻断剂的情况下的增殖或鸟苷3 '，5'-环一磷酸（cGMP）水平来确定。用NO合成酶抑制剂预处理细胞可降低VEGF诱导的增殖效应。细胞暴露于VEGF诱导cGMP水平显著增加。这种效果是加强超氧化物歧化酶的加入，并取消了NO合酶抑制剂。VEGF通过产生NO和cGMP积累刺激毛细血管后内皮细胞增殖。
Vascular endothelial growth factor (VEGF) is a secreted protein that is a specific growth factor for endothelial cells. We have recently demonstrated that nitric oxide (NO) donors and vasoactive peptides promoting NO-mediated vasorelaxation induce angiogenesis in vivo as well as endothelial cell growth and motility in vitro; in contrast, inhibitors of NO synthase suppress angiogenesis. In this study we investigated the role of NO in mediating the mitogenic effect of VEGF on cultured microvascular endothelium isolated from coronary postcapillary venules. VEGF induced a dose-dependent increase in cell proliferation and DNA synthesis. The role of NO was determined by monitoring proliferation or guanosine 3',5'-cyclic monophosphate (cGMP) levels in the presence and absence of NO synthase blockers. The proliferative effect evoked by VEGF was reduced by pretreatment of the cells with NO synthase inhibitors. Exposure of the cells to VEGF induced a significant increment in cGMP levels. This effect was potentiated by superoxide dismutase addition and was abolished by NO synthase inhibitors. VEGF stimulates proliferation of postcapillary endothelial cells through the production of NO and cGMP accumulation.