Action mechanism of microRNA-484 involved in myocardial fibrosis in hypertrophic cardiomyopathy
- VernacularTitle:微小RNA-484参与肥厚型心肌病心肌纤维化的机制研究
- Author:
Derong HUANG
1
;
Zhongxiu CHEN
2
;
Hongying CHEN
3
;
Xuemei CHEN
3
;
Ke DIAN
4
Author Information
1. Department of Cardiovascular Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, P. R. China
2. Department of Cardiology, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China
3. Cell and Molecular Biology Laboratory, Life Science Park, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China
4. Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China
- Publication Type:Journal Article
- Keywords:
Hypertrophic cardiomyopathy;
myocardial fibrosis;
microRNAs
- From:
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
2023;30(09):1316-1322
- CountryChina
- Language:Chinese
-
Abstract:
Objective To search for the key microRNAs (miRNAs) involved in myocardial fibrosis in hypertrophic cardiomyopathy, and to further explore the mechanisms involved in the regulation of myocardial fibrosis. Methods Forty-two patients with hypertrophic cardiomyopathy diagnosed and treated surgically in West China Hospital of Sichuan University from January 2014 to June 2018 were selected, including 29 males and 13 females, with a median age of 46 (15-69) years. In the myocardial tissue of patients with hypertrophic cardiomyopathy with different degrees of fibrosis, miRNAs with significantly different expression were screened and further verified at the cellular level. By regulating the expression of the target miRNAs, the expressions of fibrosis-related proteins and target genes were detected respectively. Finally, the target-binding relationship was verified by dual-luciferase reporter gene detection. Results miR-484 was up-regulated in severely fibrotic myocardial tissue and activated cardiac fibroblasts. After cardiac fibroblasts were activated by TGF-β1, the expression of miR-484 was significantly up-regulated, the expression of fibrosis-related proteins (CollagenⅠ, α-SMA) increased, and the expression of the target gene HIPK1 decreased (P<0.05). After inhibiting the expression of miR-484 by transfection of miR-484 antagomir, the expression of fibrosis-related proteins decreased, while expression of HIPK1 was up-regulated (P<0.05). The detection of dual luciferase reporter gene showed that the luciferase activity of the transfected WT-miRNA-484 mimics group was lower than that of the control group (P<0.05). Conclusion miR-484 is a pro-fibrotic miRNA that participates in the process of myocardial fibrosis by negatively regulating the expression of HIPK1. It can be used as a regulatory target to provide a therapeutic strategy for myocardial fibrosis.
