Antiapoptotic and Proapoptotic Signaling of Cyclophilin A in Endothelial Cells
Antiapoptotic and Proapoptotic Signaling of Cyclophilin A in Endothelial Cells
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DOI：
10.1007/s10753-012-9578-7
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发表时间：
2013-06
期刊：
影响因子：
5.1
通讯作者：
Yuan-an Wei;Y. Jinchuan;L. Yi;Wu Jun;Wang Zhongqun;Wang Cuiping
中科院分区：
文献类型：
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作者：
Yuan-an Wei;Y. Jinchuan;L. Yi;Wu Jun;Wang Zhongqun;Wang Cuiping
内皮细胞（EC）功能障碍是动脉粥样硬化发生和发展的关键事件。细胞凋亡可能导致内皮功能障碍并导致血管并发症。亲环素A（Cyclophilin A，CyPA）是动脉粥样硬化斑块中主要的活性氧诱导因子，可增强血管细胞的炎症活性。然而，CyPA诱导EC凋亡的机制尚不完全清楚。Western blot结果显示，细胞外CyPA激活了Akt和NF-κ B通路，上调了抗凋亡蛋白Bcl-2的表达。当用小干扰RNA阻断细胞内CyPA时，TNF-α诱导的EC凋亡和凋亡前蛋白caspase-3表达的作用被显著抑制。这项研究表明，CyPA可以启动抗凋亡和促凋亡信号在EC中，特别是在响应活性氧刺激。它是动脉粥样硬化治疗的潜在靶点。
Endothelial cell (EC) dysfunction is a key event in the onset and progression of atherosclerosis. Apoptosis may lead to endothelial dysfunction and contribute to vascular complications. Cyclophilin A (CyPA) is the main reactive oxygen species-induced factor that enhances the inflammatory activity of vascular cells in atherosclerotic plaques. However, the mechanism by which CyPA induces EC apoptosis is not entirely clear. Through Western blot, it demonstrated that extracellular CyPA activated the Akt and NF-κB pathway, followed by the upregulation of antiapoptotic protein Bcl-2 expression in ECs. When blocking intracellular CyPA by small interfering RNA in ECs, the effects of TNF-α-induced EC apoptosis and proapoptotic protein caspase-3 expression were significantly inhibited. This study shows that CyPA may initiate antiapoptotic and proapoptotic signaling in ECs, especially in response to reactive oxygen species stimulation. It serves as a potential target for atherosclerosis therapy.