Cardioprotective microRNAs (protectomiRs) in a pig model of acute myocardial infarction and cardioprotection by ischaemic conditioning: MiR‐450a

Nagy, Regina N. [Nagy, Regina Norma (PhD hallgató), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); HUN-REN-SE System Pharmacology Research Group (SU / FM / I / DPP); Centre for Pharmacology and Pharmaceutical Rese... (SU / KSZE); Makkos, András* [Makkos, András (orvos), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); Baranyai, Tamás [Baranyai, Tamás (Farmakológia), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); HUN-REN-SE System Pharmacology Research Group (SU / FM / I / DPP); Giricz, Zoltán [Giricz, Zoltán (Biokémia, Farmako...), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); HUN-REN-SE System Pharmacology Research Group (SU / FM / I / DPP); Szabó, Márta [Szabó, Márta (molekuláris biológia), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); Kravcsenko‐Kiss, Bernadett [Kiss, Bernadett (Farmakológia), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); HUN-REN-SE System Pharmacology Research Group (SU / FM / I / DPP); Bereczki, Zoltán [Bereczki, Zoltán András (biológia, bioinfo...), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); Centre for Pharmacology and Pharmaceutical Rese... (SU / KSZE); Ágg, Bence [Ágg, Bence (Farmakológia), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); Centre for Pharmacology and Pharmaceutical Rese... (SU / KSZE); HUN-REN-SE System Pharmacology Research Group (SU / FM / I / DPP); Puskás, László G. [Puskás, László (Molekuláris biológia), author] Institute of Genetics; Központi Laboratóriumok; Faragó, Nóra [Faragó, Nóra (molekuláris biológia), author] Institute of Genetics; Központi Laboratóriumok; Schulz, Rainer; Gyöngyösi, Mariann; Lukovic, Dominika; Varga, Zoltán V. [Varga, Zoltán (kardiovaszkuláris...), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); HCEMM-SU Cardiometabolic Immunology Research Group (SU / FM / I / DPP); HUN-REN-SE System Pharmacology Research Group (SU / FM / I / DPP); Görbe, Anikó** [Görbe, Anikó (orvostudomany), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); HUN-REN-SE System Pharmacology Research Group (SU / FM / I / DPP); Ferdinandy, Péter ✉ [Ferdinandy, Péter (Farmakológia, mol...), author] Department of Pharmacology and Pharmacotherapy (SU / FM / I); Centre for Pharmacology and Pharmaceutical Rese... (SU / KSZE); HUN-REN-SE System Pharmacology Research Group (SU / FM / I / DPP)

English Article (Journal Article) Scientific
Published: BRITISH JOURNAL OF PHARMACOLOGY 0007-1188 1476-5381 182 (2) pp. 396-416 2025
  • SJR Scopus - Pharmacology: D1
Identifiers
Fundings:
  • (NVKP-16-1-2016-0017 National Heart Program) Funder: NRDIO
  • (FK 134751) Funder: HSRF
  • (2018-1.3.1-VKE-2018-00024)
  • (K_21-139105) Funder: NRDIF
  • (ANN 107803)
  • (105555) Funder: HSRF
  • (RRF-2.3.1-21-2022-00003)
  • (2019-1.1.1-PIACI-KFI-2019-00367)
  • (2020-1.1.5-GYORSÍTÓSÁV-2021-00011)
  • (UNKP-20-5)
  • (ÚNKP-23-4-II-SE-34)
  • (János Bolyai Research Scholarship)
Cardioprotective miRNAs (protectomiRs) are promising therapeutic tools. Here, we aimed to identify protectomiRs in a translational porcine model of acute myocardial infarction (AMI) and to validate their cardiocytoprotective effect.Experimental ApproachProtectomiR candidates were selected after systematic analysis of miRNA expression changes in cardiac tissue samples from a closed‐chest AMI model in pigs subjected to sham operation, AMI and ischaemic preconditioning, postconditioning or remote preconditioning, respectively. Cross‐species orthologue protectomiR candidates were validated in simulated ischaemia–reperfusion injury (sI/R) model of isolated rat ocardiomyocytes and in human AC16 cells as well. For miR‐450a, we performed target prediction and analysed the potential mechanisms of action by GO enrichment and KEGG pathway analysis.Key ResultsOut of the 220 detected miRNAs, four were up‐regulated and 10 were down‐regulated due to all three conditionings versus AMI. MiR‐450a and miR‐451 mimics at 25 nM were protective in rat cardiomyocytes, and miR‐450a showed protection in human cardiomyocytes as well. MiR‐450a has 3987 predicted mRNA targets in pigs, 4279 in rats and 8328 in humans. Of these, 607 genes are expressed in all three species. A total of 421 common enriched GO terms were identified in all three species, whereas KEGG pathway analysis revealed 13 common pathways.Conclusion and ImplicationsThis is the first demonstration that miR‐450a is associated with cardioprotection by ischaemic conditioning in a clinically relevant porcine model and shows cardiocytoprotective effect in human cardiomyocytes, making it a promising drug candidate. The mechanism of action of miR‐450a involves multiple cardioprotective pathways.LINKED ARTICLESThis article is part of a themed issue Non‐coding RNA Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.2/issuetoc
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2025-04-25 06:29