A Dysregulated MicroRNA-26a/EphA2 Axis Impairs Endothelial Progenitor Cell Function via the p38 MAPK/VEGF Pathway
A Dysregulated MicroRNA-26a/EphA2 Axis Impairs Endothelial Progenitor Cell Function via the p38 MAPK/VEGF Pathway
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失调的 microRNA-26a/EphA2 轴通过 p38 MAPK/VEGF 通路损害内皮祖细胞功能
DOI：
10.1159/000369713
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
He B
中科院分区：
文献类型：
--
作者：
Zuo K;Zhi K;Zhang X;Lu C;Wang S;Li M;He B
背景：循环内皮祖细胞（EPCs）功能障碍与心血管疾病的发生有关。循环microRNAs（microRNAs）已被认为是新的生物标志物和潜在的治疗靶点。在此，我们研究了miR-26 a过表达在动脉粥样硬化中的作用，并探讨了潜在的机制。方法：从动脉粥样硬化患者和健康对照者中获得EPCs。将骨髓（BM）来源的EPCs暴露于缺氧以模拟动脉粥样硬化环境，并通过qRT-PCR和蛋白质印迹法测量miR-26 a、EphA 2和p38 MAPK水平，并通过酶联免疫吸附测定法测定VEGF水平。使用MTT测定评估细胞活力，并且荧光素酶活性测定证实EphA 2是miR-26 a的靶标。结果：动脉粥样硬化患者中miR-26 a过表达，并与EPC功能障碍相关。EphA 2被鉴定为miR-26 a的直接靶点。过表达miR-26 a下调EphA 2并损害EPC功能，而敲低miR-26 a上调EphA 2并逆转缺氧诱导的EPC功能障碍。miR-26 a过表达或敲低可调节EPCs中p38 MAPK活性和VEGF水平。结论：miR-26 a在动脉粥样硬化中的作用是通过其靶点EphA 2介导的，其机制涉及p38 MAPK/VEGF通路。
Background: Dysfunction of circulating endothelial progenitor cells (EPCs) is associated with the onset of cardiovascular disorders. Circulating microRNAs (miRNAs) have been recognized as novel biomarkers and potential therapeutic targets. Here, we examined the role of miR-26a overexpression in atherosclerosis and explored the underlying mechanisms. Methods: EPCs were obtained from patients with atherosclerosis and healthy controls. Bone marrow (BM)-derived EPCs were exposed to hypoxia to mimic the atherosclerotic environment and miR-26a, EphA2 and p38 MAPK levels were measured by qRT-PCR and western blotting, and VEGF levels were determined by enzyme linked immunosorbent assay. Cell viability was assessed using the MTT assay, and luciferase activity assays confirmed EphA2 as a target of miR-26a. Results: MiR-26a was overexpressed in patients with atherosclerosis and associated with EPC dysfunction. EphA2 was identified as a direct target of miR-26a. Overexpression of miR-26a downregulated EphA2 and impaired EPC function, whereas knockdown of miR-26a upregulated EphA2 and reversed hypoxia-induced EPC dysfunction. MiR-26a overexpression or knockdown modulated the activity of p38 MAPK and the levels of VEGF in EPCs. Conclusions: The role of miR-26a in atherosclerosis is mediated by its target EphA2 via a mechanism involving the p38 MAPK/VEGF pathway.
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影响因子：
3.1
作者：
Na Zhou;Wei-Dong Zhao;Dong-Xin Liu;Yue Liang;Wen-Gang Fang;Bo Li;Yu-hua Chen
通讯作者：
Na Zhou;Wei-Dong Zhao;Dong-Xin Liu;Yue Liang;Wen-Gang Fang;Bo Li;Yu-hua Chen
DOI：
10.1016/j.healun.2009.05.005
发表时间：
2009-09
期刊：
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
影响因子：
--
作者：
B. Wong;M. Rahmani;Zongshu Luo;B. Yanagawa;D. Wong;Honglin Luo;B. McManus
通讯作者：
B. Wong;M. Rahmani;Zongshu Luo;B. Yanagawa;D. Wong;Honglin Luo;B. McManus
影响因子：
11.8
作者：
Wang, Shusheng;Aurora, Arin B.;Johnson, Brett A.;Qi, Xiaoxia;McAnally, John;Hill, Joseph A.;Richardson, James A.;Bassel-Duby, Rhonda;Olson, Eric N.
通讯作者：
Olson, Eric N.
DOI：
10.1096/fj.04-3647fje
发表时间：
2005-10
期刊：
The FASEB Journal
影响因子：
--
作者：
Meri M. Vihanto;Jan A. Plock;Dominique Erni;Brigitte M. Frey;Felix J. Frey;U. Huynh-Do
通讯作者：
Meri M. Vihanto;Jan A. Plock;Dominique Erni;Brigitte M. Frey;Felix J. Frey;U. Huynh-Do
影响因子：
5.6
作者：
Leeper, Nicholas J.;Raiesdana, Azad;Kojima, Yoko;Chun, Hyung J.;Azuma, Junya;Maegdefessel, Lars;Kundu, Ramendra K.;Quertermous, Thomas;Tsao, Philip S.;Spin, Joshua M.
通讯作者：
Spin, Joshua M.