Qin Bing, Cao Yuze, Yang Huan, Xiao Bo, 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.
Mol Cell Biochem. 2015 Jul;405(1-2):115-24. doi: 10.1007/s11010-015-2403-5. Epub 2015 Apr 17.
Endothelial cells (ECs) apoptosis induced by oxidized low-density lipoprotein (ox-LDL) is thought to play an essential role in atherosclerosis. MicroRNAs (miRNAs) are a class of short non-coding RNAs, acting as posttranscriptional regulators of protein-coding genes involved in vascular cell biology. MiRNA-221 and miRNA-222 (miR-221/222) are known to be involved in the regulation of endothelial inflammation and angiogenesis. However, the function of miR-221/222 in ox-LDL-induced ECs apoptosis and atherosclerosis is still unknown. Here, we showed that miR-221/222 expression was markedly down-regulated in ox-LDL-induced apoptotic human umbilical cord vein endothelial cells. MiR-221/222 inhibition enhanced apoptosis in ECs, whereas over-expression of miR-221/222 could partly alleviate apoptotic cell death mediated by ox-LDL through suppression of Ets-1 and its downstream target p21. These findings suggest that manipulation of the miR-221/222-Ets-1-p21 pathway may offer a novel strategy for treatment of endothelial apoptosis and atherosclerosis.
氧化型低密度脂蛋白（ox-LDL）诱导的内皮细胞（ECs）凋亡被认为在动脉粥样硬化中起重要作用。微小RNA（miRNAs）是一类短的非编码RNA，作为参与血管细胞生物学的蛋白质编码基因的转录后调节因子。已知miRNA-221和miRNA-222（miR-221/222）参与内皮炎症和血管生成的调节。然而，miR-221/222在ox-LDL诱导的ECs凋亡和动脉粥样硬化中的功能仍不清楚。在此，我们表明在ox-LDL诱导的凋亡人脐静脉内皮细胞中，miR-221/222表达明显下调。抑制miR-221/222可增强ECs凋亡，而miR-221/222过表达可通过抑制Ets-1及其下游靶点p21部分减轻ox-LDL介导的凋亡细胞死亡。这些发现表明，调控miR-221/222-Ets-1-p21通路可能为治疗内皮细胞凋亡和动脉粥样硬化提供一种新策略。
