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Journal of cellular biochemistry
02, 2020;121 (2): 1747-1758.

MicroRNA-19a attenuates hypoxia-induced cardiomyocyte apoptosis by downregulating NHE-1 expression and decreasing calcium overload.

Jiaqi Ma, Zhangwei Chen, Yuanji Ma, Yan Xia, Kai Hu, You Zhou, Ao Chen, Juying Qian, Junbo Ge
Author Information
  1. Jiaqi Ma: Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
  2. Zhangwei Chen: Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
  3. Yuanji Ma: Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
  4. Yan Xia: Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
  5. Kai Hu: Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
  6. You Zhou: Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
  7. Ao Chen: Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
  8. Juying Qian: Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China. ORCID
  9. Junbo Ge: Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
PMID: 31633225 DOI: 10.1002/jcb.29411

Abstract

miR-19a has been shown to be involved in coronary microvascular obstruction injury; however, the underlying molecular mechanisms remain unknown. In our study, we tried to explore the role of miR-19a in cardiomyocyte apoptosis and calcium overload in vivo and in vitro induced by hypoxia. We established the acute myocardial infarction (AMI) rat model by ligating the left anterior descending artery. The expression of miR-19a in the infarct zone of AMI rats and myocardial tissue in the same position in sham rats was analyzed using RT-qPCR while Na /H exchanger 1 (NHE-1) was detected by Western blotting. We also observed the effects of overexpressing miR-19a or administering an NHE-1 inhibitor (cariporide) on hypoxia-induced (HI) calcium overload and apoptosis in primary cardiomyocytes. In addition, dual-luciferase reporter assays were conducted to investigate the potential target of miR-19a on NHE-1. Decreased miR-19a expression, as well as increased apoptosis and NHE-1 expression, were observed in the AMI model. Furthermore, after hypoxia stimulation, miR-19a was gradually reduced as time increased in primary cardiomyocytes. Overexpressing miR-19a using mimics ameliorated the increase in NHE-1 in hypoxic cardiomyocytes and thereby reduced the HI cell calcium overload and cell apoptosis rate from 12.32% to 9.5% (P < .01). In addition, the dual-luciferase reporter gene assay results verified that NHE-1 was the direct target of miR-19a. Our findings suggest that miR-19a activation can attenuate HI cardiomyocyte apoptosis by downregulating NHE-1 expression and decreasing calcium overload.

Keywords

NHE-1 apoptosis calcium overload cardiomyocytes hypoxia microRNA-19a

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MeSH Term

Animals
Apoptosis
Calcium
Cell Proliferation
Cells, Cultured
Hypoxia
Male
MicroRNAs
Myocardial Reperfusion Injury
Myocytes, Cardiac
Oxygen
Rats
Rats, Sprague-Dawley
Sodium-Hydrogen Exchangers

Chemicals

MIRN19 microRNA, rat
MicroRNAs
Sodium-Hydrogen Exchangers
growth factor-activatable Na-H exchanger NHE-1
Oxygen
Calcium
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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