PhD Scientific Days 2020

Theoretical and Translational I. Posters

NLRP3-independent Inflammasome Activation in Heart Failure

Előadó neve

Dr. Zsofia, Onodi

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, Semmelweis University

Előadó telefonszáma

+36707767852

Előadó e-mail címe

onodi.zsofia@med.semmelweis-univ.hu

Az előadás címe

NLRP3-independent Inflammasome Activation in Heart Failure

Szerző(k) neve és munkahelye

Zsofia Onodi1,2; Mihaly Ruppert3; Petra Nadasdi1,2; Przemyslaw Leszek4; Aniko Gorbe2,5; Peter Ferdinandy2,5; Tamas Radovits3; Zoltan V. Varga1,2,5

1 HCEMM-SU Cardiometabolic Immunology Group, Budapest
2 Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest
3 Heart and Vascular Center, Semmelweis University, Budapest
4 Department of Heart Failure and Transplantology, Cardinal Stefan Wyszyński Institute of Cardiology, Warszawa
5 Pharmahungary Group, Szeged

Szekció

Theoretical and Translational I. Posters

Language of the presentation

Hungarian

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Molecular Sciences

Összefoglaló szövege

Introduction: Inflammation and cytokine release is considered an important feature of progressive heart failure. Canakinumab, a monoclonal antibody against interleukin-1 β (IL-1β), has been shown to provide benefit against cardiovascular events, suggesting that blockade of IL-1β secretion and signaling might be a promising new therapeutic target. Therefore, we aimed to assess inflammasome activation in end-stage failing human hearts to identify the exact source of IL-1β in the failing heart.
Methods and Results: Inflammasomes were analyzed by immunoblot and immunohistochemistry in end-stage failing human hearts. To investigate the molecular background of inflammasome activation in cardiac tissues, cell culture experiments were performed on AC16 human cardiac and THP-1 human monocytic cell lines.
Results: Expression of the inflammasome protein absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) increased in heart failure regardless of the etiology. There was a robust infiltration of monocytes/macrophages in all groups of failing hearts, in which cells AIM2 expression was confirmed. In vitro AIM2 inflammasome activation in THP-1 cells, as well as vesicular transfer of the inflammasome adaptor protein ASC, was reduced significantly by the pharmacological blockade of pannexin-1 channels, with the clinically used uricosuric drug probenecid.
Conclusions: This is the first demonstration that AIM2 and NLRC4 inflammasome activation contribute to chronic inflammation in heart failure. Our findings suggest that repurposing probenecid is a promising strategy to reduce inflammasome activation in chronic heart failure.

Additional Information

Supervisor: Zoltan V. Varga MD, PhD
Email: varga.zoltan@med.semmelweis-univ.hu

Bemutatás módja

Poszter

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2853

Start

11:26

End

11:29

Authors (legacy)

Zsofia Onodi1,2; Mihaly Ruppert3; Petra Nadasdi1,2; Przemyslaw Leszek4; Aniko Gorbe2,5; Peter Ferdinandy2,5; Tamas Radovits3; Zoltan V. Varga1,2,5

1 HCEMM-SU Cardiometabolic Immunology Group, Budapest
2 Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest
3 Heart and Vascular Center, Semmelweis University, Budapest
4 Department of Heart Failure and Transplantology, Cardinal Stefan Wyszyński Institute of Cardiology, Warszawa
5 Pharmahungary Group, Szeged