PhD Scientific Days 2022

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Interleukin-1ß blockade improves cardiac diastolic function, but does not ameliorate key features of NASH in an aged mouse model

Előadó neve

Dr. Kucsera, Dániel

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36305717252

Előadó e-mail címe

kucsera.daniel@med.semmelweis-univ.hu

Az előadás címe

Interleukin-1ß blockade improves cardiac diastolic function, but does not ameliorate key features of NASH in an aged mouse model

Szerző(k) neve és munkahelye

Dániel Kucsera 1,2,3; Viktória E. Tóth 1,2,3; Nabil V. Sayour 1,2,3; Mihály Ruppert 4; Tamás Radovits 4; Alexandra Fábián 4; Attila Kovács 4; Béla Merkely 4; Péter Ferdinandy 1,5; Zoltán V. Varga 1,2,3

1 Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary;
2 HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary;
3 MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary;
4 Heart and Vascular Center, Semmelweis University, Budapest, Hungary;
5 Pharmahungary Group, Szeged, Hungary

Bemutatás módja

Poszter

Szekció

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Language of the presentation

Hungarian

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Introduction: Non-alcoholic steatohepatitis (NASH) is a chronic, age-related inflammatory disease of the liver. IL- 1ß is a key mediator of systemic inflammation-driven aging (aka. inflamm-aging), deteriorating cardiovascular and metabolic functions. Therefore, blocking IL-1ß and related signaling is a potential therapeutic target in these pathologies.
Aims: We aimed to investigate the hepatic and cardiac effects of anti-IL-1ß monoclonal antibody treatment in an aged mouse model of NASH.
Method: Aged male C57Bl/6J mice were fed with control (CON) diet or choline deficient (CDAA) diet and were treated with isotype control or anti-IL-1ß mAb for 8 weeks. Cardiac functions were assessed by echocardiography and subsequent strain analysis. Liver samples were analyzed by immunohistochemistry and qRT-PCR.
Results: Echocardiography revealed improved cardiac diastolic function in anti-IL-1ß treated aged mice with NASH. Histological and gene expression analyses showed marked hepatic fibrosis in CDAA fed group, but IL-1ß inhibition only affected fibrosis beneficially on the molecular level. Hepatic inflammatory changes were not affected beneficially by IL-1 blockade. Immunohistochemistry and qRT-PCR analyses of PCNA showed marked hepatocyte proliferation in CDAA fed animals, that was not influenced by IL-1β neutralization. IL-1ß inhibition led to increased hepatic expression of Pd-1 and Ctla4, while in the CDAA fed aged group, we found increased expression of Pd-l1.
Conclusion: IL-1ß inhibition improved cardiac diastolic function; however, it did not ameliorate inflammation and fibrosis in NASH, and even promoted expression of hepatic immune-checkpoints, potentially giving rise to malignant transformation, along with the NASH related hepatocellular proliferation.
Funding:
European Union’s Horizon 2020 Research and Innovation Programme no. 739593.
Momentum Research Grant LP-2021-14.
National Heart Program NVKP_16-1-2016-0017.
Higher Education Institutional Excellence Programme of the Ministry for Innovation and Technology in Hungary TKP/ITM/NKFIH.
National Research, Development and Innovation Office of Hungary OTKA-FK-134751.
New National Excellence Program of the Ministry of Human Capacities ÚNKP-21-3-II.
Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése EFOP-3.6.3.-VEKOP-16-2017-00009

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Zoltán Varga, MDm PhD

Publication of my abstract

I 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

6055

Start

10:40

End

10:45

Authors (legacy)

Dániel Kucsera 1,2,3; Viktória E. Tóth 1,2,3; Nabil V. Sayour 1,2,3; Mihály Ruppert 4; Tamás Radovits 4; Alexandra Fábián 4; Attila Kovács 4; Béla Merkely 4; Péter Ferdinandy 1,5; Zoltán V. Varga 1,2,3

1 Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary;
2 HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary;
3 MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary;
4 Heart and Vascular Center, Semmelweis University, Budapest, Hungary;
5 Pharmahungary Group, Szeged, Hungary