PhD Scientific Days 2026

Poster Session 3.H - Pharmaceutical Sciences and Health Technologies

miR-450a as a Cardioprotective MicroRNA: Validation and Mechanism of Action

Name of the presenter

Szabó, Márta

Institute/workplace of the presenter

Semmelweis University - Department of Pharmacology and Pharmacotherapy

Authors

Márta Szabó¹, Boglárka Frankó¹, Regina Nagy¹, Áron Gyovai², András Makkos², Zoltán Bereczki¹, Bence Ágg², Anikó Görbe², Péter Ferdinandy²
1: 1Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1085 Budapest, Hungary; 2Center for Pharmacology and Drug Research & Development, Semmelweis University, H-1085 Budapest, Hungary
2: 1Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1085 Budapest, Hungary; 2Center for Pharmacology and Drug Research & Development, Semmelweis University, H-1085 Budapest, Hungary; 3Pharmahungary Group, H-6722 Szeged, Hungary

Text of the abstract

Introduction: Acute myocardial infarction (AMI) is a leading cause of death worldwide, however, an effective pharmacotherapy for ischemia-reperfusion (I/R) injury remains an unmet medical need. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally and have emerged as promising multi-target therapeutic candidates. Using a translational porcine AMI model, we previously identified cardioprotective miRNAs, termed ProtectomiRs, among which miR-450a was selected for further investigation.
Aims: This study aimed to validate the cardioprotective effects of miR-450a across species and to explore the molecular pathways underlying its action.
Methods: ProtectomiR candidates identified in a clinically relevant porcine AMI model were validated in neonatal rat cardiomyocytes (NRCM) and AC16 human cardiomyocytes exposed to simulated I/R. Cells were treated with miR-450a mimic across a concentration range (0.75-100 nM), and cell viability was assessed. Predicted targets were identified using miRNAtarget™ software, followed by Gene Ontology and KEGG pathway enrichment analyses.
Results: miR-450a showed a concentration-dependent protective effect in both NRCM and AC16 cells under simulated I/R conditions. A concentration of 25 nM significantly improved cell viability, while protective effects were also observed at lower concentrations. Bioinformatic analyses identified SMAD2, DAPK2 and SOD2 among the predicted targets, linking miR-450a to TGF-β signalling, apoptosis and redox regulation. Enrichment analysis further highlighted mTOR and phosphatidylinositol signalling pathways, suggesting effects on key cell survival processes.
Conclusion: miR-450a shows cardioprotective effects in both rat and human cardiomyocytes, through the regulation of cell survival-related signalling pathways. These findings support the further development of miR-450a as a potential therapeutic candidate against I/R injury.
Funding: This work was supported by the SE250+ Excellence PhD Scholarship (Semmelweis University), the National Research, Development and Innovation Office (NKFIH, Hungary; K139237 to A.G.), and projects RRF-2.3.1-21-2022-00003, TKP2021-EGA-23, 2024-1.2.3-HU-RIZONT-2024-00026, and 2020-1.1.5-GYORSÍTÓSÁV-2021-00011, with additional support from the European Union and the Semmelweis Lendület 2024 Program.