Knockdown of miR-384-3p Protects Against Myocardial Ischemia-Reperfusion Injury in Rats Through Targeting HSP70

Authors

  • Chusheng Huang Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Zhuang Autonomous Region, China
  • Hailong Deng Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Zhuang Autonomous Region, China
  • Wen Zhao Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Zhuang Autonomous Region, China
  • Lei Xian Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning City, Guangxi Zhuang Autonomous Region, China

DOI:

https://doi.org/10.1532/hsf.3449

Keywords:

MiR-384-3p, HSP70, Ischemia-reperfusion, Myocardial infarction, apoptosis

Abstract

Background: Myocardial infarction (MI) and heart failure remain critical states of heart disease with high mortality. Previous studies have indicated that miRNA has cardioprotective effects and can resist myocardial ischemia–reperfusion (I/R) injury. However, the role of mir-384-3p in MI has not been reported, and whether this miRNA can regulate the apoptosis of cardiomyocytes needs to be verified.

Methods: The effect of hypoxia–reperfusion (H/R) on cardiomyocyte activity was detected using MTT assay. MiR-384-3p was knocked down or overexpressed in cardiomyocytes H/R models by pretreatment with miR-384-3p mimic or inhibitor to verify the function of miR-384-3p in H/R. Circulating levels of miR-384-3p was detected by quantitative realtime PCR, and protein expression was detected by western blotting. TUNEL staining and flow cytometry demonstrated a high degree of myocardium apoptosis after H/R induction. Dual-Luciferase Reporter Assay detected dynamic expression of miR-384-3p and HSP70. The infarction size of I/R rats was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining.

Results: MiR-384-3p was closely related to cardiomyocyte activity in H/R progression. Increased expression of mir-384-3p can promote the production of cleaved caspase-3 and cleaved PARP, thereby regulating cardiomyocyte apoptosis. HSP70 was a target of miR-384-3p and HSP70 silencing aggravated H/R-induced cardiomyocyte dysfunction. In an animal model, the expression level of HSP70 is regulated by miR-384-3p, and miR-384-3p inhibition remarkably reduced I/R-induced MI in rats.

Conclusion: In conclusion, the present report identified that HSP70 was a potential target of miR-384-3p, and miR-384-3p inhibition remarkably reduced I/R-induced MI in rats. Therefore, this study provides a novel therapeutic approach for the treatment of MI from bench to clinic.

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Published

2021-02-15

How to Cite

Huang, C. ., Deng, H. ., Zhao, W. ., & Xian, L. (2021). Knockdown of miR-384-3p Protects Against Myocardial Ischemia-Reperfusion Injury in Rats Through Targeting HSP70. The Heart Surgery Forum, 24(1), E143-E150. https://doi.org/10.1532/hsf.3449

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Section

Articles