Hui Lin1, Sunlei Pan1, Liping Meng2, Changzuan Zhou1, Chengjian Jiang2, Zheng Ji2, Jufang Chi3, Hangyuan Guo4. 1. The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China. 2. Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang, China. 3. Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang, China. Electronic address: jf_chi@163.com. 4. The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China; Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang, China. Electronic address: ghangyuan@hotmail.com.
Abstract
BACKGROUND: Angiotensin II (Ang II)-induced damage to endothelial cells (ECs) plays a crucial role in the pathogenesis of atherosclerosis. This study aimed to investigate the role of microRNA-384 (miR-384) in endothelial cell apoptosis. METHODS: The expression of five various miRNAs in Ang II-treated human umbilical vein endothelial cells (HUVECs) were detected by qPCR. The Ang II-induced apoptosis of HUVECs was determined by flow cytometry, TUNEL staining and western blot. Endoplasmic reticulum (ER) stress markers were detected by western blot analysis. The target gene of miR-384 was determined by bioinformatics analyses. qPCR, western blotting and immunofluorescence were performed to determine the expression level of homocysteine inducible ER protein with ubiquitin like domain 1 (Herpud1). RESULTS: miR-384 expression level was significantly decreased in Ang II-treated HUVECs. Ang II-induced HUVEC apoptosis was accompanied by the occurrence of ER stress. A decreased rate of HUVEC apoptosis and a decreased rate of ER stress were observed following restoration of miR-384 expression. Herpud1 expression level was increased in HUVECs treated with Ang II, and miR-384 mimics effectively inhibited Herpud1 expression. Mechanistically, miR-384 directly targets the 3'-untranslated region of Herpud1. Furthermore, effects of miR-384 on HUVECs apoptosis and ER stress were at least partly reversed by knockdown of Herpud1 expression. CONCLUSION: The results of the present study collectively indicated that miR-384 expression level was downregulated in Ang II-treated HUVECs and miR-384 overexpression protected HUVECs against Ang II-induced apoptosis by negatively regulating Herpud1. These findings point towards new strategies by which apoptosis of ECs can be suppressed.
BACKGROUND:Angiotensin II (Ang II)-induced damage to endothelial cells (ECs) plays a crucial role in the pathogenesis of atherosclerosis. This study aimed to investigate the role of microRNA-384 (miR-384) in endothelial cell apoptosis. METHODS: The expression of five various miRNAs in Ang II-treated human umbilical vein endothelial cells (HUVECs) were detected by qPCR. The Ang II-induced apoptosis of HUVECs was determined by flow cytometry, TUNEL staining and western blot. Endoplasmic reticulum (ER) stress markers were detected by western blot analysis. The target gene of miR-384 was determined by bioinformatics analyses. qPCR, western blotting and immunofluorescence were performed to determine the expression level of homocysteine inducible ER protein with ubiquitin like domain 1 (Herpud1). RESULTS:miR-384 expression level was significantly decreased in Ang II-treated HUVECs. Ang II-induced HUVEC apoptosis was accompanied by the occurrence of ER stress. A decreased rate of HUVEC apoptosis and a decreased rate of ER stress were observed following restoration of miR-384 expression. Herpud1 expression level was increased in HUVECs treated with Ang II, and miR-384 mimics effectively inhibited Herpud1 expression. Mechanistically, miR-384 directly targets the 3'-untranslated region of Herpud1. Furthermore, effects of miR-384 on HUVECs apoptosis and ER stress were at least partly reversed by knockdown of Herpud1 expression. CONCLUSION: The results of the present study collectively indicated that miR-384 expression level was downregulated in Ang II-treated HUVECs and miR-384 overexpression protected HUVECs against Ang II-induced apoptosis by negatively regulating Herpud1. These findings point towards new strategies by which apoptosis of ECs can be suppressed.