MiR-27a-3p/Hoxa10 Axis Regulates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Targeting Kv4.3 Expression

Frontiers in Pharmacology

Ruiting Wang¹  Xuefeng Cao²  Baoqun Li³  Xiaoyan Guo³  Jian Zhou³  Chong Pang³  Shufang Mao³  Shi Ding³  Cui Li³  Liang Zhao³  Na Guo³  Weichao Shan⁴  Yu Wang⁵  Jing Liang⁶  Zheng Zhang⁷  Yu Liu⁸  Wenya Ma⁹ 

[1]Academic Affairs, Chengde Medical College, Chengde, China

[2]Department of Anesthesiology, Affiliated Hospital of Chengde Medical College, Chengde, China

[3]Department of Basic Medicine, Chengde Medical College, Chengde, China

[4]Department of Cardiology, Affiliated Hospital of Chengde Medical College, Chengde, China

[5]Department of Pediatric Orthopedics, Affiliated Hospital of Chengde Medical College, Chengde, China

[6]State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

[7]The First Affiliated Hospital of Harbin Medical University, Harbin, China

[8]The Forth Affiliated Hospital of Harbin Medical University, Harbin, China

[9]The Second Affiliated Hospital of Harbin Medical University, Harbin, China

关键词: cardiac hypertrophy;    electrical remodeling;    HOXA10;    miRNA-27a-3p;    Ang II;   

DOI  :  10.3389/fphar.2021.680349

来源: DOAJ

【 摘 要 】

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases, which is often accompanied with structural and electrical remodeling, and can even lead to sudden cardiac death. However, its molecular mechanism still remains largely unknown. Here, we induced cardiomyocyte hypertrophy by angiotensin II (Ang II), and found that miR-27a-3p and hypertrophy-related genes were up-regulated. Further studies showed that miR-27a-3p-inhibitor can alleviate myocardial hypertrophy and electrical remodeling. Moreover, luciferase assay confirmed that miR-27a-3p could regulate the expression of downstream Hoxa10 at the transcriptional level by targeting at its 3′UTR. At the same time, the protein expression of Hoxa10 was significantly reduced in Ang II-treated cardiomyocytes. Furthermore, overexpression of Hoxa10 can reverse myocardial hypertrophy and electrical remodeling induced by Ang II in cardiomyocytes. Finally, we found that Hoxa10 positively regulated the expression of potassium channel protein Kv4.3 which was down-regulated in hypertrophic cardiomyocytes. Taken together, our results revealed miR-27a-3p/Hoxa10/Kv4.3 axis as a new mechanism of Ang II-induced cardiomyocyte hypertrophy, which provided a new target for clinical prevention and treatment of cardiac hypertrophy and heart failure.

【 授权许可】

Unknown