MicroRNA Modulation in Myocardial Ischemia-Reperfusion Injury

MicroRNAs are small non-coding RNAs that modulate gene expression post-transcriptionally and have emerged as master regulators of myocardial ischaemia-reperfusion injury. During ischaemia and subsequent reperfusion the abrupt restoration of blood flow leads to oxidative stress, calcium overload, inflammation and cardiomyocyte apoptosis. Dysregulated microRNAs influence multiple pathways including apoptosis, mitochondrial dynamics, endoplasmic reticulum stress and extracellular matrix remodelling. Specific microRNAs such as miR-21, miR-24-3p, miR-93 and miR-181a attenuate reperfusion-induced cell death by targeting effectors in the FAS/FADD, PTEN/Akt and PDCD4/BID axes. Other microRNAs regulate matrix metalloproteinases and proteoglycans to mitigate adverse remodelling and preserve ventricular function. Advances in high-throughput sequencing and omics approaches are accelerating discovery of novel ‘protectomiRs’ with translational potential as biomarkers and therapeutics. Ongoing challenges include optimising delivery systems, avoiding off-target effects and defining context-dependent roles across species and comorbidities. Nevertheless, microRNA modulation represents a promising avenue towards cardioprotection and improved outcomes after myocardial infarction.

Research from Nature Portfolio

Recent studies have shown that miR-181a acts as a critical regulator of mitochondrial fission and apoptosis in myocardial infarction models. In mice subjected to coronary artery occlusion and reperfusion, up-regulation of miR-181a inhibited cardiomyocyte apoptosis and preserved left ventricular function by directly targeting programmed cell death protein 4 (PDCD4). Modulation of PDCD4 influenced BID recruitment to the mitochondria, revealing a novel mitochondrial apoptosis axis under transcriptional control of p53. These findings elucidate a miRNA-mediated pathway and suggest miR-181a as a potential therapeutic or preventive target in ischaemic heart disease.

MicroRNA Modulation in Myocardial Ischemia-Reperfusion Injury publication trend

The graph below shows the total number of articles in microrna modulation in myocardial ischemia-reperfusion injury across all publications each year (not limited to Nature Index journals).

Technical terms

MicroRNA: small non-coding RNA that regulates gene expression at the post-transcriptional level.

Ischaemia-Reperfusion Injury: tissue damage resulting from restoration of blood flow after a period of oxygen deprivation.

Apoptosis: programmed cell death characterised by specific morphological and biochemical features.

Mitochondrial fission: division of mitochondria influencing cell survival and apoptotic signalling.

Matrix metalloproteinases (MMPs): enzymes that degrade extracellular matrix components and modulate tissue remodelling.

Proteoglycan: protein–carbohydrate complex in the extracellular matrix affecting structural integrity and signalling.

PDCD4: programmed cell death protein 4, a pro-apoptotic factor targeted by microRNAs.

FAS-mediated apoptosis: cell death pathway initiated by FAS receptor activation and its ligand.

References

1. Identification of New, Translatable ProtectomiRs against Myocardial Ischemia/Reperfusion Injury and Oxidative Stress: The Role of MMP/Biglycan Signaling Pathways. Antioxidants (2024).
2. MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4. Scientific Reports (2024).
3. MiR-21 attenuates FAS-mediated cardiomyocyte apoptosis by regulating HIPK3 expression. Bioscience Reports (2023).
4. MicroRNA-93 inhibits ischemia-reperfusion induced cardiomyocyte apoptosis by targeting PTEN. Oncotarget (2016).