PhD Scientific Days 2022
Budapest, 6-7 July 2022
Pharmaceutical Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)
Investigation of Cardiotoxicity by Dipeptidyl-peptidase-4 Inhibitors in a Human Cardiomyocyte Cell Line as well as in Samples from Chronic Heart Failure Patients
Előadó neve
Dr. Vörös, Imre
Előadó munkahelye
Semmelweis University Department of Pharmacology and Pharmacotherapy
Előadó telefonszáma
+36 20 2131 636
Előadó e-mail címe
voros.imre@med.semmelweis-univ.hu
Az előadás címe
Investigation of Cardiotoxicity by Dipeptidyl-peptidase-4 Inhibitors in a Human Cardiomyocyte Cell Line as well as in Samples from Chronic Heart Failure Patients
Szerző(k) neve és munkahelye
Imre Vörös1,2,3, Zsófia Onódi1,2,3, Viktória Éva Tóth1,2,3, Tamás Gergely1,2,3, Éva Sághy1, Anikó Görbe1,4, Ágnes Kemény5,6,7, Przemyslaw Leszek8, Zsuzsanna Helyes5,6,9, Péter Ferdinandy1,4, Zoltán V. Varga1,2,3*
1Cardiometabolic Research Group and MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary;
2HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary;
3MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary;
4Pharmahungary Group, Szeged, Hungary;
5Szentágothai János Research Centre, University of Pécs, Pécs, Hungary;
6Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary;
7Department of Medical Biology, University of Pécs, Pécs, Hungary;
8Department of Heart Failure and Transplantology, Cardinal Stefan Wyszyński National Institute of Cardiology, Warszawa, Poland;
9PharmInVivo Ltd. Pécs, Hungary
Bemutatás módja
Poszter
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: Dipeptidyl-peptidase-4 (DPP4) inhibitors are novel medicines of diabetes. The SAVOR-TIMI-53 clinical trial revealed an increased heart failure (HF)-associated hospitalization in saxagliptin-treated patients. Although this side effect could limit the therapeutic use, the mechanism of this potential cardiotoxicity is unclear. Aims: We aimed to establish a cellular platform to investigate DPP4 inhibition, and the role of its neuropeptide substrates Substance P (SP) and Neuropeptide Y (NPY), and to determine the expression of DDP4 and its neuropeptide substrates in the human heart. Methods: Western blot, radio-, enzyme-linked immuno- and RNA Scope assays were performed to investigate the expression of DPP4 and its substrates in human hearts. Calcein-based viability measurements and scratch assays were used to test the potential toxicity of DPP4 inhibitors. Results: Cardiac expression of DPP4 and NPY decreased in HF patients. In human hearts DPP4 mRNA is detectable mainly in cardiomyocytes and endothelium. Treatment with DPP4 inhibitors alone/in combination with neuropeptides didn’t affect viability but in scratch assays neuropeptides decreased, while saxagliptin co-administration increased fibroblast migration in isolated neonatal rat cardiomyocyte-fibroblast co-culture. Conclusion: Decreased DPP4 activity takes part in the pathophysiology of end-stage HF. DPP4 compensates against the elevated sympathetic activity and altered neuropeptide tone. Its inhibition decreases this adaptive mechanism, thereby exacerbating myocardial damage. Funding: ÚNKP-21-3-II-SE-14, EFOP-3.6.3-VEKOP-16-2017-00009, János Bolyai Research Scholarship (ÉS, and ZVV), NVKP-16-1-2016-0017, 2017-1.2.1-NKP-2017-00002, NKFIA: FK134751 (ZVV), K139237 (AG), European Union’s Horizon 2020 Programme (no. 739593), Momentum Research Grant (LP-2021-14 to ZVV), VEKOP-2.3.3-15-2016-00016, 2020-4.1.1.-TKP2020, TKP2021-EGA/TKP2021-NVA/TKP2021-NKTA, TKP2021-EGA-16, TKP2021-EGA-13, and 2020-1.1.6-JÖVŐ-2021-00013.
University and Doctoral School
Semmelweis University, Doctoral School of Pharmaceutical Sciences
Supervisor
Dr. Zoltán 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
poszter
Előadás fájl jóváhagyás
nem rendelkezett róla
Előadó
6017
Start
12:45
End
12:50
Authors (legacy)
Imre Vörös1,2,3, Zsófia Onódi1,2,3, Viktória Éva Tóth1,2,3, Tamás Gergely1,2,3, Éva Sághy1, Anikó Görbe1,4, Ágnes Kemény5,6,7, Przemyslaw Leszek8, Zsuzsanna Helyes5,6,9, Péter Ferdinandy1,4, Zoltán V. Varga1,2,3*
1Cardiometabolic Research Group and MTA-SE System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary;
2HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary;
3MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary;
4Pharmahungary Group, Szeged, Hungary;
5Szentágothai János Research Centre, University of Pécs, Pécs, Hungary;
6Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary;
7Department of Medical Biology, University of Pécs, Pécs, Hungary;
8Department of Heart Failure and Transplantology, Cardinal Stefan Wyszyński National Institute of Cardiology, Warszawa, Poland;
9PharmInVivo Ltd. Pécs, Hungary