Qin Bing, Shu Yaqing, Xiao Li, Lu Tingting, Lin Yinyao, Yang Huan, Lu Zhengqi
Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, People's Republic of China.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
Mol Cell Biochem. 2017 May;429(1-2):45-58. doi: 10.1007/s11010-016-2935-3. Epub 2017 Jan 21.
Atherosclerosis, a chronic inflammatory disease, is the major cause of life-threatening complications such as myocardial infarction and stroke. Endothelial cells (ECs) apoptosis plays a vital role in the initiation and progression of atherosclerosis. Although a subset of microRNAs (miRNAs) have been identified as critical regulators of atherosclerosis, studies on their participation in endothelial apoptosis in atherosclerosis have been limited. In the current study, we show that miRNA-150 (miR-150) expression was substantially up-regulated during the oxidized low-density lipoprotein (ox-LDL)-induced apoptosis in human umbilical cord vein endothelial cells (HUVECs). Forced expression of miR-150 enhanced apoptosis in ECs, whereas inhibition of miR-150 could partly alleviate apoptotic cell death mediated by ox-LDL. Further analysis identified ELK1 as a direct target of miR-150, and ELK1 knockdown abolished the anti-apoptotic effect of miR-150 inhibitor. These findings reveal a novel role of miR-150 in endothelial apoptosis and indicate a therapeutic potential of miR-150 for endothelial dysfunction and atherosclerosis.
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并发症的主要原因。内皮细胞(ECs)凋亡在动脉粥样硬化的发生和发展中起着至关重要的作用。尽管已鉴定出一部分微小RNA(miRNAs)是动脉粥样硬化的关键调节因子,但关于它们参与动脉粥样硬化中内皮细胞凋亡的研究仍然有限。在本研究中,我们发现,在氧化型低密度脂蛋白(ox-LDL)诱导的人脐静脉内皮细胞(HUVECs)凋亡过程中,miRNA-150(miR-150)的表达显著上调。强制表达miR-150可增强内皮细胞凋亡,而抑制miR-150可部分减轻ox-LDL介导的凋亡细胞死亡。进一步分析确定ELK1是miR-150的直接靶点,敲低ELK1可消除miR-150抑制剂的抗凋亡作用。这些发现揭示了miR-150在内皮细胞凋亡中的新作用,并表明miR-150对内皮功能障碍和动脉粥样硬化具有治疗潜力。