Pharmaceutical Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)
Benczik, Bettina, MSc
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine
+36309929832
benczik.bettina@med.semmelweis-univ.hu
MicroRNA and Messenger RNA Transcriptomics of Ischemic Post-conditioning Responders and Non-responders in Rat: Identification of Novel Cardioprotective Targets
Bettina Benczik1,2, Bence Ágg1,2, Rolf Schreckenberg3, Rainer Schulz3, Péter Bencsik4, Klaus-Dieter Schlüter3, Péter Ferdinandy1,2
1Cardiometabolic and MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2Pharmahungary Group, Szeged, Hungary
3Department of Physiology, Justus Liebig-University, Gießen, Germany
4Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
Poszter
Pharmaceutical Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)
English
Pharmaceutical Sciences
Introduction: Ischemic pre-conditioning (IPre) and post-conditioning (IPoC) are promising cardioprotective maneuvers. We have recently shown that while IPre is a well-reproducible effective intervention, in response to IPoC intervention, significant number of non-responder animals were detected. The molecular background underlying IPoC responder and non-responder phenotypes is not known.
Aims: We aimed to reveal key regulators in these cardioprotective maneuvers by utilizing unbiased network theoretical analysis of microRNA (miRNA) transcriptomics.
Methods: Small RNA sequencing data and qRT-PCR data were used from our previous rat cardioprotection study (Schreckenberg et al, J Cell Mol Med 2020) for further analysis. Sham, ischemia-reperfusion (I/R), IPre, IPoC responder (IPoC-R) and IPoC non-responder (IPoC-NR) groups were differentiated. Our bioinformatics workflow consisted of the following steps for comprehensive analysis of the transcriptomics datasets: differential expression analysis to identify miRNAs with changed expression patterns; principal component analysis (PCA), PERMANOVA test and hierarchical clustering to explore group miRNA dissimilarities; network theoretical target prediction by miRNAtarget™ software of differentially expressed miRNAs to indicate important interacting partners.
Result: In the different groups 185 miRNAs with significantly changed (q < 0.05) expression patterns were identified. It was found that miRNA expression profiles reflect differences between IPoC-R and IPoC-NR characteristics. Possible targets of miRNAs selected based on predefined expression patterns were predicted. With messenger RNA (mRNA) expression dataset, several of these predictions were successfully validated in silico.
Conclusion: This is the first demonstration that the IPoC-R and IPoC-NR groups have transcriptional differences both at the miRNA and mRNA levels. Moreover, miRNAs and mRNAs associated with responsiveness and non-responsiveness were identified. After experimental validation, these miRNAs and their mRNA targets may serve as biomarkers or therapeutic targets for cardioprotection.
Funding: This study was supported by Thematic Excellence Programme (2020-4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development and Bioimaging thematic programmes of the Semmelweis University.
Semmelweis University, Doctoral School of Pharmaceutical Sciences
Dr. Ferdinandy Péter, Dr. Ágg Bence
I do not give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
poszter
nem rendelkezett róla
6896
13:00
13:05
Bettina Benczik1,2, Bence Ágg1,2, Rolf Schreckenberg3, Rainer Schulz3, Péter Bencsik4, Klaus-Dieter Schlüter3, Péter Ferdinandy1,2
1Cardiometabolic and MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2Pharmahungary Group, Szeged, Hungary
3Department of Physiology, Justus Liebig-University, Gießen, Germany
4Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary