期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/ijms22179539
关键词
network theory; cardioprotection; vasculoprotection; microRNA; miRNA; Rictor
资金
- National Research, Development and Innovation Office of Hungary (NKFIA) [NVKP-16-1-2016-0017, OTKA-FK 134751, VEKOP-2.3.2-16-2016-00002]
- Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary
- Hungarian (OTKA)
- Austrian Science Funds (FWF) [FWF I 1277]
- European Union [739593]
- Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic
- Slovak Academy of Sciences VEGA [2/0104/20]
- New National Excellence Program of the Ministry of Human Capacities [UNKP-19-3-I-SE-60]
- New National Excellence Program of the Ministry for Innovation and Technology from the National Research, Development and Innovation Fund [UNKP-20-5, UNKP-20-4-I-SE-7]
- Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences
- ministry of innovation and technology from national research, development and innovation fund
- NRDI Fund [2019-1.1.1-PIACI-KFI-2019-00367]
- Thematic Excellence Program of the Ministry for Innovation and Technology in Hungary [2020-4.1.1.-TKP2020]
- EU COST Action [BM1203]
- CardioRNA.eu action [CA16225]
- Cardioprotection.eu action [CA17129]
This study aimed to identify key molecular targets of ProtectomiRs and confirm their association with cardioprotection. The results demonstrated that Rictor is the central molecular target of ProtectomiRs and may be a potential novel drug target for acute cardioprotection.
Cardioprotective medications are still unmet clinical needs. We have previously identified several cardioprotective microRNAs (termed ProtectomiRs), the mRNA targets of which may reveal new drug targets for cardioprotection. Here we aimed to identify key molecular targets of ProtectomiRs and confirm their association with cardioprotection in a translational pig model of acute myocardial infarction (AMI). By using a network theoretical approach, we identified 882 potential target genes of 18 previously identified protectomiRs. The Rictor gene was the most central and it was ranked first in the protectomiR-target mRNA molecular network with the highest node degree of 5. Therefore, Rictor and its targeting microRNAs were further validated in heart samples obtained from a translational pig model of AMI and cardioprotection induced by pre- or postconditioning. Three out of five Rictor-targeting pig homologue of rat ProtectomiRs showed significant upregulation in postconditioned but not in preconditioned pig hearts. Rictor was downregulated at the mRNA and protein level in ischemic postconditioning but not in ischemic preconditioning. This is the first demonstration that Rictor is the central molecular target of ProtectomiRs and that decreased Rictor expression may regulate ischemic postconditioning-, but not preconditioning-induced acute cardioprotection. We conclude that Rictor is a potential novel drug target for acute cardioprotection.
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