Division of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
Biochem Biophys Res Commun. 2010 Apr 16;394(4):976-80. doi: 10.1016/j.bbrc.2010.03.102. Epub 2010 Mar 20.
Angiogenesis and apoptosis are reciprocal processes in endothelial cells. Bcl-2, an anti-apoptotic protein, has been found to have angiogenic activities. The purpose of this study was to determine the role of Bcl-2 in hypoxia-induced angiogenesis in endothelial cells and to investigate the underlying mechanisms. Human aortic endothelial cells (HAECs) were exposed to hypoxia followed by reoxygenation. Myocardial ischemia and reperfusion mouse model was used and Bcl-2 expression was assessed. Bcl-2 expression increased in a time-dependent manner in response to hypoxia from 2 to 72h. Peak expression occurred at 12h (3- to 4-fold, p<0.05). p38 inhibitor (SB203580) blocked hypoxia-induced Bcl-2 expression, whereas PKC, ERK1/2 and PI3K inhibitors did not. Knockdown of Bcl-2 resulted in decreased HAECs' proliferation and migration. Over-expression of Bcl-2 increased HAECs' tubule formation, whereas knockdown of Bcl-2 inhibited this process. In this model of myocardial ischemia and reperfusion, Bcl-2 expression was increased and was associated with increased p38 MAPK activation. Our results showed that hypoxia induces Bcl-2 expression in HAECs via p38 MAPK pathway.
血管生成和细胞凋亡是内皮细胞中相互作用的两个过程。Bcl-2 是一种抗凋亡蛋白，已经被发现具有血管生成活性。本研究旨在确定 Bcl-2 在缺氧诱导的内皮细胞血管生成中的作用，并探讨其潜在机制。将人主动脉内皮细胞（HAECs）暴露于缺氧环境中，然后再进行复氧处理。使用心肌缺血再灌注小鼠模型来评估 Bcl-2 的表达情况。结果显示，Bcl-2 的表达随缺氧时间呈时间依赖性增加，从 2 小时到 72 小时。12 小时时达到峰值（增加 3-4 倍，p<0.05）。p38 抑制剂（SB203580）阻断了缺氧诱导的 Bcl-2 表达，而 PKC、ERK1/2 和 PI3K 抑制剂则没有。Bcl-2 敲低导致 HAECs 的增殖和迁移减少。Bcl-2 的过表达增加了 HAECs 的管腔形成，而 Bcl-2 的敲低则抑制了这一过程。在心肌缺血再灌注模型中，Bcl-2 的表达增加，与 p38 MAPK 激活增加有关。我们的研究结果表明，缺氧通过 p38 MAPK 通路诱导 HAECs 中 Bcl-2 的表达。
