MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis.
MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis.
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MicroRNA-26a 在动脉粥样硬化的情况下通过直接靶向 TRPC6 来防止内皮细胞凋亡。
DOI：
10.1038/srep09401
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发表时间：
2015-03-24
影响因子：
4.6
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Zhang Y;Qin W;Zhang L;Wu X;Du N;Hu Y;Li X;Shen N;Xiao D;Zhang H;Li Z;Zhang Y;Yang H;Gao F;Du Z;Xu C;Yang B
动脉粥样硬化是一种慢性炎症性疾病，是心肌梗死和中风等危及生命的并发症的主要原因。内皮细胞凋亡在动脉粥样硬化病变的发生和发展中起着重要作用。虽然一个小分子RNA（microRNAs，miRs）亚类已被鉴定为动脉粥样硬化的关键调节因子，但关于其参与动脉粥样硬化内皮细胞凋亡的研究还很有限。在我们的研究中，我们发现miR-26 a在高脂饮食（HFD）喂养的ApoE−/−小鼠的主动脉内膜中表达显著降低。用氧化低密度脂蛋白（ox-LDL）处理人主动脉内皮细胞（HAECs）抑制miR-26 a表达。MTT法和TUNEL染色结果显示，miR-26 a的强制表达抑制了内皮细胞凋亡。进一步的分析确定TRPC 6是miR-26 a的靶点，并且TRPC 6过表达消除了miR-26 a的抗凋亡作用。此外，发现细胞溶质钙和线粒体凋亡途径介导miR-26 a对内皮细胞凋亡的有益作用。总之，我们的研究揭示了miR-26 a在内皮细胞凋亡中的新作用，并表明miR-26 a对与凋亡性细胞死亡相关的动脉粥样硬化具有治疗潜力。
Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke. Endothelial apoptosis plays a vital role in the initiation and progression of atherosclerotic lesions. Although a subset of microRNAs (miRs) have been identified as critical regulators of atherosclerosis, studies on their participation in endothelial apoptosis in atherosclerosis have been limited. In our study, we found that miR-26a expression was substantially reduced in the aortic intima of ApoE−/− mice fed with a high-fat diet (HFD). Treatment of human aortic endothelial cells (HAECs) with oxidized low-density lipoprotein (ox-LDL) suppressed miR-26a expression. Forced expression of miR-26a inhibited endothelial apoptosis as evidenced by MTT assay and TUNEL staining results. Further analysis identified TRPC6 as a target of miR-26a, and TRPC6 overexpression abolished the anti-apoptotic effect of miR-26a. Moreover, the cytosolic calcium and the mitochondrial apoptotic pathway were found to mediate the beneficial effects of miR-26a on endothelial apoptosis. Taken together, our study reveals a novel role of miR-26a in endothelial apoptosis and indicates a therapeutic potential of miR-26a for atherosclerosis associated with apoptotic cell death.
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影响因子：
9
作者：
通讯作者：
--
DOI：
10.1161/01.atv.17.12.3588
发表时间：
1997-12-01
影响因子：
8.7
作者：
Hermann, C;Zeiher, AM;Dimmeler, S
通讯作者：
Dimmeler, S
MicroRNA-26A通过靶向BMP/SMAD1信号来调节病理和生理血管生成。
影响因子：
20.1
作者：
Icli B;Wara AK;Moslehi J;Sun X;Plovie E;Cahill M;Marchini JF;Schissler A;Padera RF;Shi J;Cheng HW;Raghuram S;Arany Z;Liao R;Croce K;MacRae C;Feinberg MW
通讯作者：
Feinberg MW
影响因子：
8.5
作者：
Li, Z.;Xu, J.;Yang, Z.
通讯作者：
Yang, Z.
影响因子：
6.4
作者：
Jia, Ling-Fei;Wei, Su-Bi;Yu, Guang-Yan
通讯作者：
Yu, Guang-Yan