Dexpramipexole attenuates myocardial ischemia/reperfusion injury through upregulation of mitophagy

Lu Tang; Yun-Peng Li; Juan Hu; Ai-Hua Chen; Yingli Mo

doi:10.1016/j.ejphar.2021.173962

Dexpramipexole attenuates myocardial ischemia/reperfusion injury through upregulation of mitophagy

Eur J Pharmacol. 2021 May 15:899:173962. doi: 10.1016/j.ejphar.2021.173962. Epub 2021 Feb 19.

Authors

Lu Tang¹, Yun-Peng Li², Juan Hu¹, Ai-Hua Chen³, Yingli Mo⁴

Affiliations

¹ Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
² Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Gongye Road, Guangzhou, 510280, China; Department of Cardiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450000, China.
³ Department of Cardiology, Zhujiang Hospital of Southern Medical University, No. 253, Gongye Road, Guangzhou, 510280, China. Electronic address: aihuachenzjphd@hotmail.com.
⁴ Department of Internal Medicine, Yiyang Medical College, Yingbin Road 516, Yiyang, Hunan, 413000, China; Hunan Provincial Engineering and Technological Research Center for Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine and Protecting Visual Function, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China. Electronic address: 251817@stu.hnucm.edu.cn.

PMID: 33610599
DOI: 10.1016/j.ejphar.2021.173962

Abstract

Reperfusion causes undesirable damage to the ischemic myocardium while restoring the blood flow. In this study, we evaluated the effects of dexpramipexole (DPX) on myocardial injury induced by ischemia/reperfusion (I/R) in-vivo and the hypoxia/reoxygenation (HR) in-vitro and examined the functional mechanisms of DPX. DPX protected cells against H/R-induced mitochondrial dysfunction and prevented H/R damage. Both myocardial infarct size and tissue damage due to I/R was reduced upon DPX treatment. We discovered that DPX enhanced mitophagy in-vivo and in-vitro, which was accompanied by enhanced expression of PINK1 and Parkin. Knock-down of PINK1 and Parkin by specific siRNAs reversed DPX-induced inhibition of myocardial I/R injury. These findings suggest that DPX might protect against myocardial injury via PINK1 and Parkin.

Keywords: Dexpramipexole; Ischemia; Mitophagy; Myocardial; Reperfusion.

MeSH terms

Animals
Cells, Cultured
Disease Models, Animal
Male
Mice
Mice, Inbred C57BL
Mitochondria, Heart / drug effects*
Mitochondria, Heart / genetics
Mitochondria, Heart / metabolism
Mitochondria, Heart / ultrastructure
Mitophagy / drug effects*
Myocardial Infarction / genetics
Myocardial Infarction / metabolism
Myocardial Infarction / pathology
Myocardial Infarction / prevention & control*
Myocardial Reperfusion Injury / genetics
Myocardial Reperfusion Injury / metabolism
Myocardial Reperfusion Injury / pathology
Myocardial Reperfusion Injury / prevention & control*
Myocytes, Cardiac / drug effects*
Myocytes, Cardiac / metabolism
Myocytes, Cardiac / ultrastructure
Pramipexole / pharmacology*
Protein Kinases / genetics
Protein Kinases / metabolism
Protein Transport
Rats
Rats, Sprague-Dawley
Signal Transduction
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism

Substances

Pramipexole
Ubiquitin-Protein Ligases
parkin protein
Protein Kinases
PTEN-induced putative kinase