MicroRNA‑1 downregulation induced by carvedilol protects cardiomyocytes against apoptosis by targeting heat shock protein 60

Hu,Yingying; Chen,Xi; Li,Xina; Li,Zhange; Diao,Hongtao; Liu,Lu; Zhang,Jia; Ju,Jin; Wen,Lin; Liu,Xin; Pan,Zhenwei; Xu,Chaoqian; Hai,Xin; Zhang,Yong

doi:10.3892/mmr.2019.10034

MicroRNA‑1 downregulation induced by carvedilol protects cardiomyocytes against apoptosis by targeting heat shock protein 60

Authors:
- Yingying Hu
- Xi Chen
- Xina Li
- Zhange Li
- Hongtao Diao
- Lu Liu
- Jia Zhang
- Jin Ju
- Lin Wen
- Xin Liu
- Zhenwei Pan
- Chaoqian Xu
- Xin Hai
- Yong Zhang
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Affiliations: Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Pharmacology, The State‑Province Key Laboratories of Biomedicine‑Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China, Center of Chronic Diseases and Drug Research, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
Published online on: March 14, 2019 https://doi.org/10.3892/mmr.2019.10034
Pages: 3527-3536
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial infarction (MI) is the most common event in cardiovascular disease. Carvedilol, a β‑blocker with multiple pleiotropic actions, is widely used for the treatment cardiovascular diseases. However, the underlying mechanisms of carvedilol on alleviating MI are not fully understood. The aim of the present study was to investigate whether the beneficial effects of carvedilol were associated with regulation of microRNA‑1 (miR‑1). It was demonstrated that carvedilol ameliorated impaired cardiac function and decreased infarct size in a rat model of MI induced by coronary artery occlusion. Similarly, carvedilol reversed the H2O2‑induced decrease in cardiomyocyte viability in a dose‑dependent manner. The in vivo and in vitro models demonstrated the downregulation of miR‑1 following treatment with carvedilol. Overexpression of miR‑1, a known pro‑apoptotic miRNA, decreased cell viability and induced cell apoptosis. Transfection of miR‑1 abolished the beneficial effects of carvedilol. The expression of heat shock protein 60 (HSP60), a direct target of miR‑1, was identified to be decreased in MI and H2O2‑induced apoptosis, which was associated with a decrease in Bcl‑2 and an increase in Bax; expression was restored following treatment with carvedilol. It was concluded that carvedilol partially exhibited its beneficial effects by downregulating miR‑1 and increasing HSP60 expression. miR‑1 has become a member of the group of carvedilol‑responsive miRNAs. Future studies are required to fully elucidate the potential overlapping or compensatory effects of known carvedilol‑responsive miRNAs and their underlying mechanisms of action in the pathophysiology of cardiovascular diseases.

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