PhD Scientific Days 2020

Theoretical and Translational II. Posters

Network Approach to Identify Molecular Targets of Cardiac ProtectomiRs

Előadó neve

Dr. Makkos, András

Előadó munkahelye

Semmelweis University, Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36703707325

Előadó e-mail címe

makkos.andras@med.semmelweis-univ.hu

Az előadás címe

Network Approach to Identify Molecular Targets of Cardiac ProtectomiRs

Szerző(k) neve és munkahelye

András Makkos1, Ágg Bence1, Zoltán Varga1, Zoltán Giricz1, Mariann Gyöngyösi2, Anikó Görbe1, Péter Ferdinandy1,2
1. MTA-SE System Pharmacology Research Group and Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis
University, Budapest, Hungary
2. Division of Cardiology, Medical University of Vienna, Vienna, Austria.
3. Pharmahungary Group, Szeged, Hungary

Szekció

Theoretical and Translational II. Posters

Language of the presentation

Hungarian

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Molecular Sciences

Összefoglaló szövege

Background:
Protection of ischemic heart is an unmet need. We have previously found that cardiac non-coding microRNA expression fingerprint is significantly changed in the ischemic heart with or without ischemic pre- and postconditioning and identified miRNAs that are involved in cardioprotection. We termed these microRNAs ProtectomiRs. Common downstream molecular targets of ProtectomiRs may reveal potential new targets in cardioprotection.
Aim:
We aimed to identify targets modulated by ProtectomiRs based on an unbiased network theoretic approach and experimentally validate the predicted downstream targets.
Methods
Target genes regulated with high probability by ProtectomiRs were collected with miRNAtarget.com software. MicroRNA-target network was constructed and visualized based on miRNA-target interactions. After the target prediction, the microRNA target with the highest degree (RICTOR) was chosen for validation. Myocardium samples for validation were originated from a translational pig model of pre- and postconditioning in ischemia/reperfusion injury. Validation of RICTOR was performed with qRT-PCR and Western blot analysis.
Results
MicroRNA-target network analysis resulted in 882 genes ranked by interaction degree. RICTOR had degree 5, other 14 genes had degree 3, and others less than 3 degrees. Expression of RICTOR mRNA tended to decrease in ischemic postconditioning (1.000±0.151 vs. 0.618±0.134 AU; p=0.19, one-way ANOVA), and remained unchanged in ischemic preconditioning (1.000±0.151 vs. 1.369±0.381; one-way ANOVA). RICTOR protein was significantly decreased in ischemic postconditioning (0.642±0.171 vs. 0.222±0.012 AU; one-way ANOVA), and not influenced in ischemic preconditioning (0.642±0.171 vs. 0.601±0.066 AU; one-way ANOVA) with western blot analysis.
Conclusion:
Unbiased analysis of cardioprotective microRNAs and their target network revealed the common regulated protein RICTOR in ischemic conditioning. Therefore, RICTOR could be a potential target in cardioprotection

Additional Information

Supervisor: Görbe Anikó, Ferdinandy Péter
E-mail address: gorbe.aniko@med.semmelweis-univ.hu, peter.ferdinandy@med.semmelweis-univ.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1293

Start

12:56

End

12:59

Authors (legacy)

András Makkos1, Ágg Bence1, Zoltán Varga1, Zoltán Giricz1, Mariann Gyöngyösi2, Anikó Görbe1, Péter Ferdinandy1,2
1. MTA-SE System Pharmacology Research Group and Cardiovascular and Metabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis
University, Budapest, Hungary
2. Division of Cardiology, Medical University of Vienna, Vienna, Austria.
3. Pharmahungary Group, Szeged, Hungary