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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1470142
This article is part of the Research Topic Cardiometabolic Diseases: Therapeutic Targets Discovery and Mechanism Study View all 8 articles

Post-Conditioning on Myocardial Ischemia-Reperfusion Injury

Provisionally accepted
Jing Li Jing Li 1Yiyong Wei Yiyong Wei 2Yi Wang Yi Wang 3Ying Xu Ying Xu 4Huanhuan Ma Huanhuan Ma 3Lulin Ma Lulin Ma 5*Qingfan Zeng Qingfan Zeng 1*
  • 1 School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou Province, China
  • 2 Department of Anesthesiology, Longgang Maternity and Child Institute of Shantou University Medical College, Shenzhen, Guangdong Province, China
  • 3 Zunyi Medical University, Zunyi, Guizhou Province, China
  • 4 Department of Oncology, Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, China
  • 5 Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

The final, formatted version of the article will be published soon.

    Background: Acid-sensing ion channels are activated during myocardial ischemia and are implicated in the mechanism of myocardial ischemia-reperfusion injury (MIRI). Acid-sensing ion channel 3 (ASIC3), the most pH-sensitive member of the ASIC family, is highly expressed in myocardial tissues. However, the role of ASIC3 in MIRI and its precise effects on the myocardial metabolome remain unclear. These unknowns might be related to the cardioprotective effects observed with APETx2 post-conditioning.Method: Rat hearts subjected to Langendorff perfusion were randomly assigned to the normal (Nor) group, ischemia/reperfusion (I/R) group, ASIC3 blockade (AP) group. Rat hearts in group AP were treated with the ASIC3-specific inhibitor APETx2 (630 nM). Molecular and morphological changes were observed to elucidate the role of ASIC3 in MIRI. Bioinformatics analyses identified differential metabolites and pathways associated with APETx2 post-conditioning. Results: APETx2 post-conditioning stabilized hemodynamics in the isolated rat heart model of MIRI. It also reduced myocardial infarct size, mitigated mitochondrial damage at the ultrastructural level, and improved markers of myocardial injury and oxidative stress. Further more, we observed that phosphatidylcholine, phosphatidylethanolamine, citric acid, cyanidin 5-O-beta-D-glucoside, and L-aspartic acid decreased after MIRI. The levels of these metabolites were partially restored by APETx2 post-conditioning. These metabolites are primarily involved in autophagy and endogenous cannabinoid signaling pathways. Conclusion: ASIC3 is potentially a key player in MIRI. APETx2 post-conditioning may improve MIRI through specific metabolic changes. This study provides valuable data for future research on the metabolic mechanisms underlying the effects of APETx2 post-conditioning in MIRI.

    Keywords: ASIC3, Miri, Metabolites, APETx2 post-conditioning, phospholipid metabolites

    Received: 25 Jul 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 Li, Wei, Wang, Xu, Ma, Ma and Zeng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Lulin Ma, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
    Qingfan Zeng, School of Clinical Medicine, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China

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