PhD Scientific Days 2022

Pharmaceutical Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Transcriptomic profiling of the adrenal gland in rat model of heart failure

Előadó neve

Váradi, Barnabás

Előadó munkahelye

Semmelweis University Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36209859832

Előadó e-mail címe

barnabas36@gmail.com

Az előadás címe

Transcriptomic profiling of the adrenal gland in rat model of heart failure

Szerző(k) neve és munkahelye

Barnabás Váradi1, Nabil V. Sayour1,2, Gábor B Brenner1, András Makkos1,5,6, Julianna Novák1,4, Viktória E. Tóth1,2, Bence Ágg1,5,6, Zsófia Onódi1,2, Dániel Kucsera1,2, Imre Vörös1,2, Zoltán V. Varga1,2,5, Péter Ferdinandy1,5,6
1,Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine, Budapest, Hungary
2 HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary
3 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
4 Experimental Research Laboratory, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
5 Pharmahungary Group, Szeged
6 MTA-SE System Pharmacology Research Group, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Pharmaceutical Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Language of the presentation

Hungarian

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Introduction: Heart failure is a serious health problem due its prevalence and high mortality rate. It has long been known that the adrenal gland plays a major role in the pathomechanism of heart failure through the secretion of catecholamines, glucocorticoids, and mineralocorticoids, which can be modulated pharmaceutically to reduce mortality. Nevertheless, the molecular mechanism of adrenal gland activation in heart failure is less known.
Aims: We aimed to better understand of role of the adrenal gland in chronic heart failure and effect of the currently used renin-angiotensin-aldosterone inhibitor therapy.
Methods: Male Wistar rats were randomized to chronic infarction (MI, n=6), sham operated (SHAM n=6) and enalapril treated chronic infarction (IN, n=6) groups. The chronic infarction was induced by permanent occlusion of the left anterior descending coronary artery for 6 weeks. After termination the transcriptomes of whole adrenal glands were investigated by next-generation sequencing. Gene expression profiling was perfomed by HISAT2-featureCounts-DESeq2 bioinformatical workflow. Differential expressions were tested by Wald test, where the p-values were corrected by the Benjamini-Hochberg procedure due the multiple comparisons. The gene expression profiles were analysed comprehensively by principal component analysis and hierarchical clustering and expression profiles were functionally analysed by using GeneOntology terms.
Results: Ischemic heart failure had robust effect on transcriptome of the adrenal gland, whereas the enalapril treatment had minor effect. In addition to changes related to steroid hormones and catecholamines, heart failure also induces interleukine-1 and monocyte/macrophage-mediated inflammation in the adrenal gland.
Conclusion: We have shown that heart failure induces robust changes in the adrenal transcriptome, suggesting a central role of inflammation in the disease, in addition to changes in catecholamine, glucocorticoid, and mineralocorticoid synthesis. The current “gold-standard” therapy has minor effect on all of these processes.
Funding: This project was supperted by OTKA-FK-134751, and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 739593 and by a Momentum Research Grant from the Hungarian Academy of Sciences (LP-2021-14 to ZVV). BV was supported EFOP-3.6.3-VEKOP-16-2017-00009

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Dr. Bence Ágg, Dr. Zoltán V. Varga

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

11:30

End

11:45

Authors (legacy)

Barnabás Váradi1, Nabil V. Sayour1,2, Gábor B Brenner1, András Makkos1,5,6, Julianna Novák1,4, Viktória E. Tóth1,2, Bence Ágg1,5,6, Zsófia Onódi1,2, Dániel Kucsera1,2, Imre Vörös1,2, Zoltán V. Varga1,2,5, Péter Ferdinandy1,5,6
1,Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine, Budapest, Hungary
2 HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary
3 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
4 Experimental Research Laboratory, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
5 Pharmahungary Group, Szeged
6 MTA-SE System Pharmacology Research Group, Budapest, Hungary