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Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury

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Abstract

Ischemia/reperfusion (I/R) injury is a tissue damage during reperfusion after an ischemic condition. I/R injury is induced by pathological cases including stroke, myocardial infarction, circulatory arrest, sickle cell disease, acute kidney injury, trauma, and sleep apnea. It can lead to increased morbidity and mortality in the context of these processes. Mitochondrial dysfunction is one of the hallmarks of I/R insult, which is induced via reactive oxygen species (ROS) production, apoptosis, and autophagy. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play a main regulatory role in gene expression. Recently, there are evidence, which miRNAs are the major modulators of cardiovascular diseases, especially myocardial I/R injury. Cardiovascular miRNAs, specifically miR-21, and probably miR-24 and miR-126 have protective effects on myocardial I/R injury. Trimetazidine (TMZ) is a new class of metabolic agents with an anti-ischemic activity. It has beneficial effects on chronic stable angina by suppressing mitochondrial permeability transition pore (mPTP) opening. The present review study addressed the different mechanistic effects of TMZ on cardiac I/R injury. Online databases including Scopus, PubMed, Web of Science, and Cochrane library were assessed for published studies between 1986 and 2021. TMZ, an antioxidant and metabolic agent, prevents the cardiac reperfusion injury by regulating AMP-activated protein kinase (AMPK), cystathionine-γ-lyase enzyme (CSE)/hydrogen sulfide (H2S), and miR-21. Therefore, TMZ protects the heart against I/R injury by inducing key regulators such as AMPK, CSE/H2S, and miR-21.

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Authors and Affiliations

  1. Medical Technology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mohammad Hosein Farzaei

  2. Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Fatemeh Ramezani-Aliakbari, Mohammad Zarei & Siamak Shahidi

  3. Department of Medicinal Chemistry, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Ramezani-Aliakbari

  4. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Mohammad Zarei, Alireza Komaki, Siamak Shahidi, Abdolrahman Sarihi & Iraj Salehi

  5. Department of Neuroscience, School of Sciences and Advanced Technology in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Alireza Komaki, Siamak Shahidi, Abdolrahman Sarihi & Iraj Salehi

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  1. Mohammad Hosein Farzaei
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All authors contributed to the study conception and design. Literature search and data analysis were performed by MF, FR-A, MR-A, MZ, AK, and SSh. The first draft of the manuscript was written by FR-A and critically revised by AS and IS. All authors read and approved the final manuscript.

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Farzaei, M.H., Ramezani-Aliakbari, F., Ramezani-Aliakbari, M. et al. Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury. Naunyn-Schmiedeberg's Arch Pharmacol 396, 1633–1646 (2023). https://doi.org/10.1007/s00210-023-02469-7

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