MicroRNA Modulation in Cardiac Pathologies

MicroRNAs are small non-coding RNAs that fine-tune gene expression in the heart, impacting processes such as hypertrophy, fibrosis, apoptosis and responses to ischaemia. Dysregulation of individual microRNAs can tip the balance between adaptive remodelling and pathological injury. For example, shifts in specific microRNA levels underlie the transition from compensatory hypertrophy to heart failure, while altered microRNA profiles after myocardial infarction influence inflammation, scar formation and angiogenesis. Redox-dependent chemical modification of microRNAs further diversifies their effects, enabling reactive oxygen species to reprogramme gene regulation. Interactions with long non-coding RNAs and changes in microRNA biogenesis pathways also contribute to the complex regulatory network. Insights into these mechanisms have revealed candidate biomarkers of cardiac injury, and have spurred the development of antimiR and microRNA-mimic therapeutics. Taken together, microRNA modulation represents a global axis for both mechanistic understanding and targeted intervention across a spectrum of cardiac disorders.

Research from Nature Portfolio

Recent studies have demonstrated that oxidative modification of a cardiac microRNA can directly drive fibroblast proliferation. In animal models of fibrosis and ischaemia–reperfusion injury, reactive oxygen species convert guanine residues in miR-30c to an oxidised form that mis-matches its target mRNA for the cell-cycle regulator CDKN2C, thereby unleashing fibroblast expansion. In a separate seminal work, the miR-29 family has been shown to orchestrate pathological remodelling by de-repressing Wnt signalling in cardiomyocytes. Deletion or blockade of miR-29 in pressure-overload models prevents both hypertrophy and fibrosis, highlighting cell-specific delivery of antimiR-29 as a promising therapeutic strategy.

MicroRNA Modulation in Cardiac Pathologies publication trend

The graph below shows the total number of articles in microrna modulation in cardiac pathologies across all publications each year (not limited to Nature Index journals).

Technical terms

MicroRNA: small non-coding RNA molecule 21–25 nucleotides long that regulates gene expression post-transcriptionally by base-pairing with target mRNAs.

Fibrosis: pathological process characterised by excessive deposition of extracellular matrix components, leading to tissue stiffening and dysfunction.

Hypertrophy: enlargement of cardiomyocytes or heart muscle in response to stress or injury.

Induced pluripotent stem cell (iPSC): adult somatic cell reprogrammed to resemble embryonic stem cells, enabling disease modelling and therapeutic studies.

Ischaemia/reperfusion injury: tissue damage caused by restoration of blood flow following a period of oxygen deprivation, leading to oxidative stress and inflammation.

References

1. Overview of MicroRNAs in Cardiac Hypertrophy, Fibrosis, and Apoptosis. International Journal of Molecular Sciences (2016).
2. Oxidative modification of miR-30c promotes cardiac fibroblast proliferation via CDKN2C mismatch. Scientific Reports (2024).
3. Cardiac myocyte miR-29 promotes pathological remodeling of the heart by activating Wnt signaling. Nature Communications (2017).
4. Modeling Cardiotoxicity in Pediatric Oncology Patients Using Patient-Specific iPSC-Derived Cardiomyocytes Reveals Downregulation of Cardioprotective microRNAs. Antioxidants (2023).
5. Integrated Analysis of lncRNA–miRNA–mRNA Regulatory Network in Rapamycin-Induced Cardioprotection against Ischemia/Reperfusion Injury in Diabetic Rabbits. Cells (2023).
6. miR‐31‐5p suppresses myocardial hypertrophy by targeting Nfatc2ip. Journal of Cellular and Molecular Medicine (2024).