Clusterin regulates TRPM2 to protect against myocardial injury induced by acute myocardial infarction injury

  • Tissue Cell. 2023 Jun:82:102038. doi: 10.1016/j.tice.2023.102038.
Dalei Li  1 ,  Mengying Wang  1 ,  Rong Fan  2 ,  Zeyu Song  1 ,  Zhenyuan Li  1 ,  Hailin Gan  1 ,  Huaying Fan  3
Affiliations
  • 1. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, PR China.
  • 2. Yantai Raphael Biotechnology Co., Ltd, Yantai 264005, PR China.
  • 3. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, PR China. Electronic address: [email protected].
PMID: 36870313 DOI: 10.1016/j.tice.2023.102038
Abstract

Background: Clusterin and transient receptor potential melastatin 2 (TRPM2) play significant roles in acute Myocardial Infarction (AMI), but their interactions in AMI are unclear.

Methods: Myocardial Infarction was induced by ligation of the left anterior descending coronary artery in wild-type C57BL/6J male mice. Infarct size and myocardium pathology were evaluated after 6, 12, and 24 h of ischemia. The expression levels of clusterin and TRPM2 were measured in the myocardium. Furthermore, Myocardial Infarction was induced in TRPM2 knockout (TRPM2-/-) C57BL/6J male mice to evaluate the expression of clusterin. H9C2 cells with various levels of TRPM2 expression were used to analyze the effects of clusterin under hypoxic conditions.

Results: Following AMI, myocardial hypertrophy and TRPM2 expression increased in a time-dependent manner. In contrast, the expression of clusterin decreased in an infarct time-dependent manner. Knockout of TRPM2 protected against myocardial injury and resulted in upregulation of clusterin. In the H9C2 cells, cultured under hypoxic conditions treatment with clusterin or silencing of TRPM2 significantly increased cell viability and decreased TRPM2 expression. Treatment with clusterin protected against TRPM2 overexpression-induced damage in hypoxia-treated H9C2 cells.

Conclusion: This study characterized the effects of clusterin on TRPM2 in AMI, which may guide development of new treatment strategies for AMI.

Keywords
Acute myocardial infarction; Exogenous clusterin; Infarct size; Oxidative stress; Transient receptor potential melastatin 2.
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