PhD Scientific Days 2023

Translational Medicine I.

Transcriptomic analysis of the adrenal gland in rat model of chronic heart failure

Előadó neve

Dr. Váradi, Barnabás

Neptun code

bq2irj

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, Semmelweis University

Előadó telefonszáma

+36209859832

Előadó e-mail címe

varadi.barnabas@semmelweis.hu

Az előadás címe

Transcriptomic analysis of the adrenal gland in rat model of chronic heart failure

Szerző(k) neve és munkahelye

Váradi Barnabás1,2, Tóth Viktória E.1,2,3, Brenner Gábor B.1, Makkos András1,3, Onódi Zsófia1,2,3, Kucsera Dániel1,2,3, Vörös Imre1,2,3, Novák Julianna1,2, Sayour Nabil Viktor1,2,3, Ferdinandy Péter1,4, Varga Zoltán V.1,2,3,4

1Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine, Budapest.
2HCEMM-SU Cardiometabolic Immunology Research Group, Budapest.
3HAS-SU Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest.
4Pharmahungary Group, Szeged

Bemutatás módja

Szóbeli

Szekció

Translational Medicine I.

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Due to its prevalence and high mortality rate, heart failure is a significant health burden worldwide. It is well established, that pharmaceutical modulation of mineralocorticoids, and cathecholamins in heart failure can succescfully reduce mortality. However, the molecular mechanisms leading to adrenal gland activation during heart failure are unclear.
Aims: We aimed to investigate trancriptomic alterations of adrenal gland in chronic heart failure model to better understand the mechanism of adrenal gland activation and investigate the effect of currently used renin-angiotensin-aldosterone inhibitory therapy.
Methods: Male Wistar rats were randomized to sham operated (SHAM n=6), vehicle (MI, n=6) and enalapril treated chronic infarction (IN, n=6) groups. Chronic infarction was induced by permanent left anterior descending coronary artery occlusion, which followed by echocardiographic measurements and termination 6 weeks later. Gene expression profile of adrenal glands was investigated by next-generation sequencing. Bioinformaics analysis of RNA sequences were perfomed by HISAT2-featureCounts-DESeq2 workflow. Functional changes of trancsriptomic profile were investigated using Gene Ontology terms. Correlation network was built from significant Spearman correlations between gene expression and echocardiographical parameters.
Result: Ischemic heart failure had robust effect on adrenal transcriptome (cholesterol, steroid hormones, chatelcolamins and inflammation relatead genes), which was modulated mildly by enalapril treament. Network analysis showed that numerous genes have multiple significant correlation with echocardohraphical parameters, one of which could have direct effect on the heart.
Conclusion: We demonstrated that heart failure besides modulating catecholamine and steroid hormon synthesis induce interleukin-1β, monocyte macrophage system mediated inflammation, on which the curretnly used “gold-standard” therapy has minor effect. Furthermore a potential new drug target for the treatment of heart failure was identified.
Funding: This project was supperted by no. RRF-2.3.1-21-2022-00003, OTKA-FK-134751, by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 739593, by a Momentum Research Grant from the Hungarian Academy of Sciences (LP-2021-14 to ZVV), and BV by EFOP-3.6.3-VEKOP-16-2017-00009.

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Dr. Bence Ágg, PhD; Dr. Zoltán V. Varga, PhD

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6872

Start

09:45

End

10:00

Authors (legacy)

Váradi Barnabás1,2, Tóth Viktória E.1,2,3, Brenner Gábor B.1, Makkos András1,3, Onódi Zsófia1,2,3, Kucsera Dániel1,2,3, Vörös Imre1,2,3, Novák Julianna1,2, Sayour Nabil Viktor1,2,3, Ferdinandy Péter1,4, Varga Zoltán V.1,2,3,4

1Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine, Budapest.
2HCEMM-SU Cardiometabolic Immunology Research Group, Budapest.
3HAS-SU Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest.
4Pharmahungary Group, Szeged