Journal Article

MicroRNA-29a-3p Reduces TNFα-Induced Endothelial Dysfunction by Targeting Tumor Necrosis Factor Receptor 1

Wang, Peng, Li, Ying, Deng, Xinrui, Chu, Xia, Ma, Xiaohui, Sun, Changhao, Yang, Jianjun, Wei, Chunbo

2019

Overview

miR-29a-3p has been shown to be associated with cardiovascular diseases; however, the effect of miR-29a-3p on endothelial dysfunction is unclear. This study aimed to reveal the effects and mechanisms of miR-29a-3p on endothelial dysfunction. The levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and E-selectin were determined by real-time PCR and immunofluorescence staining to reveal the degree of tumor necrosis factor alpha (TNFα)-induced endothelial dysfunction. A luciferase activity assay and cell transfection with a miR-29a-3p mimic or an inhibitor were used to reveal the underlying mechanisms of miR-29a-3p action. Furthermore, the effects of miR-29a-3p on endothelial dysfunction were assessed in C57BL/6 mice injected with TNFα and/or a miR-29a-3p agomir. The results showed that the expression of TNFα-induced adhesion molecules in vascular endothelial cells (EA.hy926 cells, human aortic endothelial cells [HAECs], and primary human umbilical vein endothelial cells [pHUVECs]) and smooth muscle cells (human umbilical vein smooth muscle cells [HUVSMCs]) was significantly decreased following transfection with miR-29a-3p. This effect was reversed by cotransfection with a miR-29a-3p inhibitor. As a key target of miR-29a-3p, tumor necrosis factor receptor 1 mediated the effect of miR-29a-3p. Moreover, miR-29a-3p decreased the plasma levels of TNFα-induced VCAM-1 (32.62%), ICAM-1 (38.22%), and E-selectin (39.32%) in vivo. These data indicate that miR-29a-3p plays a protective role in TNFα-induced endothelial dysfunction, suggesting that miR-29a-3p is a novel target for the prevention and treatment of atherosclerosis.

• Publisher: Elsevier Inc,Elsevier Limited,American Society of Gene & Cell Therapy,Elsevier
• Subject: adhesion molecules / Aorta / Arteriosclerosis / Atherosclerosis / Cardiovascular diseases / Cell adhesion & migration / Cell adhesion molecules / Coronary vessels / E-selectin / Endothelial cells / endothelial dysfunction / Experiments / Gene expression / Health care / Immunofluorescence / Intercellular adhesion molecule 1 / Medical research / MicroRNAs / miR-29a-3p / miRNA / Necrosis / Plasma levels / Protein expression / Proteins / Smooth muscle / Software / TNF-R1 / Transfection / Tumor necrosis factor receptor 1 / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Umbilical vein / Vascular cell adhesion molecule 1