Low concentrations of arsenic induce vascular endothelial growth factor and nitric oxide release and stimulate angiogenesis in vitro
Low concentrations of arsenic induce vascular endothelial growth factor and nitric oxide release and stimulate angiogenesis in vitro
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DOI：
10.1021/tx025652a
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发表时间：
2003-04-01
影响因子：
4.1
通讯作者：
Yu, HS
中科院分区：
文献类型：
--
作者：
Kao, YH;Yu, CL;Yu, HS
砷（As）在自然界中广泛分布，其在饮用水中的污染仍然是一个主要的公共卫生问题。接触砷可能导致退行性周围血管疾病。本研究的目的是阐明砷在调节人脐静脉内皮细胞 (HUVEC) 细胞增殖和体外血管生成中的作用，并仔细研究这些事件的影响因素。结果表明，较低浓度（最高 1 μM）的亚砷酸钠可刺激 HUVEC 细胞生长。体外血管生成测定表明，低浓度的砷会增加血管管的形成，而血红蛋白（一种有效的一氧化氮清除剂）会消除这种现象。相反，较高浓度的砷（> 5 μM）显示出细胞毒性和对血管生成的抑制作用。我们还证明，较低浓度的砷在转录和翻译水平上调组成型一氧化氮合酶（NOS3）的表达，并且较低浓度的砷暗示对血管内皮生长因子（VEGF）表达的调节作用。此外，低浓度的 As（
Arsenic (As) is widely distributed in nature, and its contamination in drinking water remains a major public health problem. Exposure to As may lead to degenerative peripheral vascular diseases. The purpose of this study is to clarify the role of As in modulating cell proliferation and in vitro angiogenesis in human umbilical vein endothelial cells (HUVECs) and to scrutinize the contributing factors of these events. The results revealed that lower concentrations (up to 1 muM) of sodium arsenite stimulated HUVEC cell growth. An in vitro angiogenesis assay indicated that low concentrations of As increased vascular tubular formation, which was abrogated by hemoglobin, a potent nitric oxide scavenger. In contrast, higher concentrations of As (> 5 muM) revealed cytotoxicity and inhibition to angiogenesis. We also demonstrated that lower concentrations of As upregulated the expression of constitutive nitric oxide synthase (NOS3) at both transcriptional and translational levels and that lower concentrations of As implicated a modulatory role in vascular endothelial growth factor (VEGF) expression. In addition, low concentrations of As (