title: Antiapoptotic and proapoptotic signaling of cyclophilin A in endothelial cells.
abstract: 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.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, No. 438 Jie Fang Road, Zhenjiang, Jiangsu Province, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wei
authors.forename: Yan
authors.initials: Y
authors.lastname: Jinchuan
authors.forename: Liang
authors.initials: L
authors.lastname: Yi
authors.forename: Wu
authors.initials: W
authors.lastname: Jun
authors.forename: Wang
authors.initials: W
authors.lastname: Zhongqun
authors.forename: Wang
authors.initials: W
authors.lastname: Cuiping
mesh_terms: D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism*; D053148:Caspase 3 / Q000096:biosynthesis; D002478:Cells, Cultured; D021984:Cyclophilin A / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D004789:Enzyme Activation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D021984:Cyclophilin A