miR-101-3p induces vascular endothelial cell dysfunction by targeting tet methylcytosine dioxygenase 2

• 来源期刊: 生物化学与生物物理学报（英文版）
• 关键词: endothelial cell dysfunction atherosclerosis miR-101-3p ROS TET2
• 年，卷（期）: 2020,（2）
• 页码范围: 180-191
• 页数: 12页
• 语种: 英文
• DOI: 10.1093/abbs/gmz154

摘要

Endothelial cell (EC) dysfunction represents an early key event in atherosclerosis.Recently,MicroRNAs have been demonstrated to regulate EC function.miR-101-3p has been discovered to regulate cell apoptosis and proliferation in cardiovascular diseases.Therefore,the aim of the current study was to clarify whether miR-101-3p regulates the dysfunction of vascular endothelial cells.In this study,the transfection of human umbilical vein endothelial cells (HUVECs) with miR-101-3p mimic induced reactive oxygen species (ROS) production,EC dysfunction,and activated nuclear factor-κB (NF-κB),whereas transfection with miR-101-3p inhibitor alleviated these events.The antioxidant N-acetylcysteine alleviated miR-101-3p-induced EC dysfunction.Moreover,we observed that miR-101-3p inhibited the expression of tet methylcytosine dioxygenase 2 (TET2)at the posttranscriptional level,resulting in increased ROS production and activated NF-κB.TET2 overexpression inhibited ROS production,EC dysfunction,and NF-κB activation in miR-101-3p-transfected HUVECs.These results indicate that miR-101-3p induces EC dysfunction by targeting TET2,which regulates ROS production,EC dysfunction,and NF-κB activation.Taken together,our current study reveals a novel pathway associated with EC dysfunction.The modulation of miR-101-3p and TET2 expression levels may serve as a potential target for therapeutic strategies for atherosclerosis.