Acetylated cyclophilin A is amajor mediator in hypoxia-induced autophagy and pulmonary vascular angiogenesis
Acetylated cyclophilin A is amajor mediator in hypoxia-induced autophagy and pulmonary vascular angiogenesis
复制标题
乙酰化亲环蛋白 A 是缺氧诱导的自噬和肺血管血管生成的主要介质
DOI：
10.1097/hjh.0000000000001224
复制
发表时间：
2017-04-01
影响因子：
4.9
通讯作者：
Zhu, Daling
中科院分区：
文献类型：
--
作者：
Mao, Min;Yu, Xiufeng;Zhu, Daling
背景资料：自噬是维持细胞稳态的主要细胞内降解和循环过程，参与了缺氧性肺动脉高压（HPAH）肺血管结构和功能的异常。亲环素A（Cyclophilin A，CyPA）是一种分泌型氧化应激诱导因子。方法：用电镜、免疫印迹和荧光显微镜观察慢性缺氧大鼠肺组织中自噬的变化。结果：在缺氧条件下，HPAH大鼠肺动脉内皮细胞和培养的牛肺动脉内皮细胞均出现自噬激活。抑制自噬可减弱HPAH的病理进展，并抑制内皮细胞迁移和血管生成。我们还发现CyPA在缺氧条件下上调并乙酰化，并通过与自噬蛋白5和自噬蛋白7的相互作用导致自噬的异常发生。此外，乙酰化CyPA是必不可少的过度增殖，迁移，和管形成网络的肺动脉内皮cells.Conclusion：我们的研究结果表明乙酰化CyPA的自噬和随后的肺血管新生的异常发生的关键作用。
Background: Autophagy is a major intracellular degradation and recycling process that maintains cellular homeostasis, which is involved in structural and functional abnormalities of pulmonary vasculature in hypoxic pulmonary arterial hypertension (HPAH). Cyclophilin A (CyPA) is a secreted, oxidative stress-induced factor. Its role in inducing autophagy and augmenting endothelial cell dysfunction has never been explored.Methods: Lungs from rats exposed to chronic hypoxia were examined for autophagy with electron microscopy, western blotting, and fluorescence microscopy.Results: Activated autophagy was seen in the endothelium of the pulmonary artery from experimental rat models of HPAH and cultured bovine pulmonary arterial endothelial cells under hypoxia. Inhibiting autophagy attenuated the pathological progression of HPAH and repressed endothelial cell migration and angiogenesis. We also showed that CyPA was upregulated and acetylated under hypoxia and led to the abnormal occurrence of autophagy through its interaction with autophagy protein 5 and autophagy protein 7. Moreover, acetylated CyPA was essential for the excessive proliferation, migration, and tube formation networks of pulmonary arterial endothelial cells.Conclusion: Our results indicate the crucial role of acetylated CyPA in the abnormal occurrence of autophagy and subsequent pulmonary vascular angiogenesis.