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Review
. 2025 Dec;18(6):1667-1680.
doi: 10.1007/s12265-025-10609-y. Epub 2025 Apr 8.

The Impact of Opioids on Epigenetic Modulation in Myocardial Ischemia and Reperfusion Injury: Focus on Non-coding RNAs

Mohsen Davari #  1   2 , Mahmoud Khansari #  3   2 , Sahar Hosseini  4   2 , Reza Morovatshoar  5   2 , Alireza Azani  6   2 , Seyedeh Tarlan Mirzohreh  7   2 , Mohammadjavad Ashrafi Mahabadi  4   2 , Moein Ghasemi  8   2 , Mohammad Saeed Soleimani Meigoli  9   2 , Sima Foroughi Nematollahi  10   2 , Sina Pourranjbar  10   2 , Qumars Behfar  11   12 , Mandana Baghdadi  13   14 , Ahmad Mir Hosseini  15   16
Affiliations
Review

The Impact of Opioids on Epigenetic Modulation in Myocardial Ischemia and Reperfusion Injury: Focus on Non-coding RNAs

Mohsen Davari et al. J Cardiovasc Transl Res. 2025 Dec.

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.

Keywords: Ischemia/reperfusion injury; MicroRNA; Morphine; Non-coding RNA; Opioid.

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Conflict of interest statement

Declarations. Ethics and Consent to Participate: Not applicable. Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Clinical Trial Number: Not applicable.

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