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



Davari M^{1, 13} ; Khansari M^{2, 13} ; Hosseini S^{3, 13} ; Morovatshoar R^{4, 13} ; Azani A^{5, 13} ; Mirzohreh ST^{6, 13} ; Mahabadi MA^{3, 13} ; Ghasemi M^{7, 13} ; Meigoli MSS^{8, 13} ; Nematollahi SF^{9, 13} ; Pourranjbar S^{9, 13} ; Behfar Q^{10, 13} ; Baghdadi M^{11, 13} ; Hosseini AM^{12, 13}
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.