2. Academic Validation
  3. Dexpramipexole attenuates myocardial ischemia/reperfusion injury through upregulation of mitophagy

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.
Lu Tang 1,  Yun-Peng Li 2,  Juan Hu 1,  Ai-Hua Chen 3,  Yingli Mo 4
Affiliations

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: [email protected].
  • 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: [email protected].
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.

Figures
Products