2. Academic Validation
  3. Inhibition of miR-143-3p alleviates myocardial ischemia reperfusion injury via limiting mitochondria-mediated apoptosis

Inhibition of miR-143-3p alleviates myocardial ischemia reperfusion injury via limiting mitochondria-mediated apoptosis

  • Biol Chem. 2023 Feb 14. doi: 10.1515/hsz-2022-0334.
Chuang-Hong Lu 1,  De-Xin Chen 1,  Kun Dong 2,  Yun-Jiao Wu 1,  Na Na 3,  Hong Wen 1,  Yao-Shi Hu 1,  Yuan-Ying Liang 1,  Si-Yi Wu 1,  Bei-You Lin 4,  Feng Huang 1,  Zhi-Yu Zeng 1
Affiliations

Affiliations

  • 1 Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention, Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, No.6 Shuangyong Road, Nanning 530021, Guangxi, China.
  • 2 Department of Organ Transplantation, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Nanning 530021, Guangxi, China.
  • 3 Department of Chemistry, Scripps Research Institute, No.10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • 4 Department of Cardiology, Zhuhai City People's Hospital, No.79 Kangning Road, Zhuhai 519050, Guangdong, China.
PMID: 36780323 DOI: 10.1515/hsz-2022-0334
Abstract

MicroRNA (miR)-143-3p is a potential regulatory molecule in myocardial ischemia/reperfusion injury (MI/RI), wherein its expression and pathological effects remains controversial. Thus, a mouse MI/RI and cell hypoxia/reoxygenation (H/R) models were built for clarifying the miR-143-3p's role in MI/RI. Following myocardial ischemia for 30 min, mice underwent reperfusion for 3, 6, 12 and 24 h. It was found miR-143-3p increased in the ischemic heart tissue over time after reperfusion. Cardiomyocytes transfected with miR-143-3p were more susceptible to Apoptosis. Mechanistically, miR-143-3p targeted B cell lymphoma 2 (Bcl-2). And miR-143-3p inhibition reduced cardiomyocytes Apoptosis upon H/R, whereas it was reversed by a specific Bcl-2 Inhibitor ABT-737. Of note, miR-143-3p inhibition upregulated Bcl-2 with better mitochondrial membrane potential (Δψm), reduced cytoplasmic cytochrome c (cyto-c) and Caspase proteins, and minimized infarction area in mice upon I/R. Collectively, inhibition of miR-143-3p might alleviate MI/RI via targeting Bcl-2 to limit mitochondria-mediated Apoptosis. To our knowledge, this study further clarifies the miR-143-3p's pathological role in the early stages of MI/RI, and inhibiting miR-143-3p could be an effective treatment for ischemic myocardial disease.

Keywords

B-cell lymphoma-2; apoptosis; microRNA-143-3p; mitochondria; myocardial ischemia reperfusion injury; therapeutic effect.

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