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The Impact of Opioids on Epigenetic Modulation in Myocardial Ischemia and Reperfusion Injury: Focus on Non-Coding Rnas Publisher



Davari M1, 13 ; Khansari M2, 13 ; Hosseini S3, 13 ; Morovatshoar R4, 13 ; Azani A5, 13 ; Mirzohreh ST6, 13 ; Mahabadi MA3, 13 ; Ghasemi M7, 13 ; Meigoli MSS8, 13 ; Nematollahi SF9, 13 ; Pourranjbar S9, 13 ; Behfar Q10, 13 ; Baghdadi M11, 13 ; Hosseini AM12, 13
Authors
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Authors Affiliations
  1. 1. Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  2. 2. General Surgery Department, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  5. 5. Department of Medical Genetic, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  7. 7. Faculty of Medicine, Tehran University of Medical Science, Tehran, Iran
  8. 8. School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
  9. 9. Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
  10. 10. National Institute for Health Research, Tehran University of Medical Sciences, Tehran, Iran
  11. 11. Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  12. 12. Mashhad University of Medical Sciences, Mashhad, Iran
  13. 13. Cardiology Department, Mentoring Program in Medical Sciences, MSA Research Group, Tehran, Iran

Source: Journal of Cardiovascular Translational Research Published:2025


Abstract

Myocardial ischemia–reperfusion injury (IRI) is a major issue in cardiovascular medicine, marked by tissue damage from the restoration of blood flow after ischemia. Opioids, known for their pain-relieving properties, have emerged as potential cardioprotective agents in IRI. Recent research suggests opioids influence epigenetic mechanisms—such as histone modifications and non-coding RNAs (ncRNAs)—which are essential for regulating gene expression and cellular responses during myocardial IRI. This review delves into how opioids like remifentanil affect histone modifications, DNA methylation, and ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Remifentanil postconditioning (RPC) reduces apoptosis in cardiomyocytes through histone deacetylation, specifically downregulating histone deacetylase 3 (HDAC3). Similarly, opioids impact miRNAs such as miR- 206 - 3p and miR- 320 - 3p, and lncRNAs like TINCR and UCA1, which influence apoptosis, inflammation, and oxidative stress. Understanding these interactions highlights the potential for opioid-based therapies in mitigating IRI-induced myocardial damage. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.