Role of autophagy in angiogenesis in aortic endothelial cells
Role of autophagy in angiogenesis in aortic endothelial cells
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DOI：
10.1152/ajpcell.00164.2011
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发表时间：
2012-01-01
影响因子：
5.5
通讯作者：
Shi, Yang
中科院分区：
文献类型：
--
作者：
Du, Jianhai;Teng, Ru-Jeng;Shi, Yang
杜J，滕RJ，关T，Eis A，考尔S，Konduri GG，施Y.自噬在主动脉内皮细胞血管生成中的作用。Am J Physiol Cell Physiol 302：C383-C391，2012.首次发表于2011年10月26日; doi：10.1152/ajpcell.00164.2011。血管生成在缺血性心脏病和外周血管疾病的恢复阶段起着关键作用。自噬的增加在缺氧和慢性缺血条件下具有保护作用。在本研究中，我们确定了自噬在血管生成中的作用。3-用甲基腺嘌呤（3-MA）和针对ATG 5的小干扰RNA（siRNA）抑制营养剥夺诱导的牛主动脉内皮细胞（BAECs）自噬。BAECs管形成和细胞迁移的测定显示，通过3-MA或针对ATG 5的siRNA抑制自噬减少血管生成。与此相反，诱导自噬过度表达的ATG 5增加BAECs管的形成和迁移。此外，抑制自噬损害血管内皮生长因子（VEGF）诱导的血管生成。然而，自噬的抑制并没有改变促血管生成因子如VEGF、血小板衍生生长因子或整合素α V的表达。此外，自噬增加了活性氧（ROS）的形成并激活了AKT磷酸化。自噬的抑制显着降低ROS的产生和AKT的激活，但不是细胞外调节激酶，而ATG 5的过表达增加细胞内ROS的产生和AKT的激活BAECs。抑制AKT活化或ROS产生显著降低了由ATG 5过表达诱导的管形成。在这里，我们报告了一个新的观察，自噬在BAEC血管生成中起着重要作用。诱导自噬促进血管生成，而抑制自噬抑制血管生成，包括VEGF诱导的血管生成。ROS的产生和AKT的激活可能是自噬介导血管生成的重要机制。我们的研究结果表明，靶向自噬可能为治疗心血管疾病提供一个重要的新工具。
Du J, Teng RJ, Guan T, Eis A, Kaul S, Konduri GG, Shi Y. Role of autophagy in angiogenesis in aortic endothelial cells. Am J Physiol Cell Physiol 302: C383-C391, 2012. First published October 26, 2011; doi:10.1152/ajpcell.00164.2011.-Angiogenesis plays critical roles in the recovery phase of ischemic heart disease and peripheral vascular disease. An increase in autophagy is protective under hypoxic and chronic ischemic conditions. In the present study we determined the role of autophagy in angiogenesis. 3-Methyladenine (3-MA) and small interfering RNA (siRNA) against ATG5 were used to inhibit autophagy induced by nutrient deprivation of cultured bovine aortic endothelial cells (BAECs). Assays of BAECs tube formation and cell migration revealed that inhibition of autophagy by 3-MA or siRNA against ATG5 reduced angiogenesis. In contrast, induction of autophagy by overexpression of ATG5 increased BAECs tube formation and migration. Additionally, inhibiting autophagy impaired vascular endothelial growth factor (VEGF)-induced angiogenesis. However, inhibition of autophagy did not alter the expression of pro-angiogenesis factors such as VEGF, platelet-derived growth factor, or integrin alpha V. Furthermore, autophagy increased reactive oxygen species (ROS) formation and activated AKT phosphorylation. Inhibition of autophagy significantly decreased the production of ROS and activation of AKT but not of extracellular regulated kinase, whereas overexpression of ATG5 increased cellular ROS production and AKT activation in BAECs. Inhibition of AKT activation or ROS production significantly decreased the tube formation induced by ATG5 overexpression. Here we report a novel observation that autophagy plays an important role in angiogenesis in BAECs. Induction of autophagy promotes angiogenesis while inhibition of autophagy suppresses angiogenesis, including VEGF-induced angiogenesis. ROS production and AKT activation might be important mechanisms for mediating angiogenesis induced by autophagy. Our findings indicate that targeting autophagy may provide an important new tool for treating cardiovascular disease.