Pharmaceutical Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)
Regina Norma, Nagy, MSc
Semmelweis University, Department of Pharmacology and Pharmacotherapy
+36204339806
nagy.regina@phd.semmelweis.hu
Identification of cardioprotective miRNAs (protectomiRs) in a porcine model of acute myocardial infarction and cardioprotection by ischemic conditioning
Regina N. Nagy1,2, András Makkos1, Tamás Baranyai1, Zoltán Giricz1, Bernadett Kiss1,2, László G. Puskás3, Nóra Faragó3, Dominika Lukovic4, Mariann Gyöngyösi4, Anikó Görbe1,5, Péter Ferdinandy1,5
1 Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2 MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
3 Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary
4 Department of Cardiology, Medical University of Vienna, Vienna, Austria
5 Pharmahungary Group, Szeged, Hungary
Szóbeli
Pharmaceutical Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)
English
Pharmaceutical Sciences
Introduction: We have previously identified cardioprotective microRNAs, protectomiRs, by a systematic analysis of miRNA expression pattern in myocardial infarction and cardioprotection induced by ischemic conditioning in rats. ProtectomiRs may be important therapeutics for cardioprotection.
Aims: To identify protectomiRs in a porcine model of acute myocardial infarction (AMI) and cardioprotection and validate their cardiocytoprotective effect.
Methods: In our previous study, pigs were subjected to sham operation, ischemia/reperfusion (AMI) and preconditioning (IPreC), postconditioning (IPostC), or remote perconditioning (RIPerC). MiRNA expression pattern of infarcted region of the left ventricles was detected by qPCR. Potential protectomiRs were selected by systematic comparison of expression changes due to different conditioning stimuli vs. AMI. To validate the cardiocytoprotective effect of selected miRNAs their mimics or inhibitors (antagomiRs) were transfected in isolated rat cardiomyocytes, and the survival of cells was measured after simulated ischemia/reperfusion injury.
Results: Expression of 57 microRNAs changed by IPreC, 54 by IPostC and 68 by RIPerC vs. AMI. Expression of 14 microRNAs changed significantly due to all three conditionings vs. AMI (10 downregulated and 4 upregulated miRNAs). Rat homologs of these protectomiR candidates were identified and 12 showed 100% sequence homology with the original pig miRNAs. These miRNAs (8 antagomiRs, 4 miRNA mimics) were transfected in rat cardiomyocytes. Modulation of 2 mimics of these miRNAs significantly improved the survival of cells after ischemia/reperfusion injury (due to intellectual property protection, we do not disclose the protectomiRs here).
Conclusion: Here we identified 2 protectomiRs in a clinically relevant porcine model of AMI that can be potential therapeutic molecules.
Funding: National Research, Development and Innovation Office of Ministry of Innovation and Technology in Hungary (NKFIA; NVKP-16-1-2016-0017 National Heart Program, OTKA-FK134751, OTKA-K139237, Research Excellence Program). Thematic Excellence Programme (2020-4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, Therapeutic Development programs of the Semmelweis University. EU COST action. MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University.
Semmelweis University, Doctoral School of Theoretical and Translational Medicine
Dr. Anikó Görbe
I do not give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
szóbeli
nem rendelkezett róla
6888
11:45
12:00
Regina N. Nagy1,2, András Makkos1, Tamás Baranyai1, Zoltán Giricz1, Bernadett Kiss1,2, László G. Puskás3, Nóra Faragó3, Dominika Lukovic4, Mariann Gyöngyösi4, Anikó Görbe1,5, Péter Ferdinandy1,5
1 Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2 MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
3 Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary
4 Department of Cardiology, Medical University of Vienna, Vienna, Austria
5 Pharmahungary Group, Szeged, Hungary