PhD Scientific Days 2019

Budapest, April 25–26, 2019

Inflammasome activation in end-stage failing heart

Gulyás-Ónodi, Zsófia

Zsofia Onodi1, Mihaly Ruppert2, Przemyslaw Leszek3, Viktoria Eva Toth1, Gabor Koncsos1, Tamas Radovits2, Peter Ferdinandy1, Zoltan V Varga1
1Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest
2Heart and Vascular Center, Semmelweis University, Budapest
3Department of Heart Failure and Transplantology, Cardinal Stefan Wyszyński Institute of Cardiology, Warszawa

Language of the presentation


Text of the abstract

Background: Inflammation and cytokine release is considered an important feature of progressive heart failure. Canakinumab, a monoclonal antibody against interleukin-1b (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. Inflammasome activation is the main contributor to IL-1β maturation; nevertheless, the role of inflammasome activation in chronic heart failure is unknown. Therefore, we aimed to assess inflammasome activation in myocardial samples from end-stage failing human hearts.
Methods: Inflammasome activation was measured by immunobloting in left ventricular tissue samples harvested from end-stage failing human hearts. Monocytes and macrophages in human left ventricles were detected by immunohistochemistry. To investigate the molecular background of inflammasome activation, a series of cell culture experiments were performed on AC16 human cardiomyocytes and THP-1 human monocytic cell lines.
Results: Expression of AIM2 and NLRC4 increased in end-stage human failings hearts regardless of the etiology of heart failure. There was a robust infiltration of Iba1+ monocytes/macrophages in all groups of failing hearts. In vitro AIM2 inflammasome activation, as induced by transfection with double-stranded DNA [poly(deoxyadenylic-deoxythymidylic)] was reduced significantly by the pharmacological blockade of pannexin-1 channels.
Conclusions: AIM2 and NLRC4 inflammasome activation might contribute to chronic inflammation in heart failure. Our findings suggest that pannexin-1 channels might be a promising novel target to reduce inflammasome activation. We also hypothesize that cell death during the remodeling process associates with the release of damage-associated molecules (dsDNA, mtDNA, HMGB1), that in turn activate AIM2 inflammasome, ultimately leading to the chronic inflammatory reaction.

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Doctoral School of Pharmaceutical Sciences
Experimental and Clinical Pharmacology
Supervisor: Zoltan Varga (e-mail: