PhD Scientific Days 2025

Poster Session I. - I: Theoretical and Translational Medicine

Investigation of Inflammasome Activity in a Rodent Model of Decompensated Heart Failure

Name of the presenter

Tóth Artúr

Institute/workplace of the presenter

Department of Pharmacology and Pharmacotherapy, Semmelweis University

Authors

Artúr Tóth¹, Dr. Dávid Nagy², Dr. Zsófia Gulyás-Onódi³, Márton Kocsis³, Dr. Tímea Bálint², Dr. Attila Oláh², Dr. Alex Ali Sayour², Dr. Bálint András Barta², Prof. Dr. Béla Merkely², Prof. Dr. Péter Ferdinandy³, Prof. Dr. Tamás Radovits², Dr. Zoltán V. Varga³, Dr. Mihály Ruppert²

1: Department of Pharmacology and Pharmacotherapy
2: Heart and Vascular Centre, Semmelweis University
3: Department of Pharmacology and Pharmacotherapy, Semmelweis University

Text of the abstract

Introduction: Inflammation is a key component of the pathomechanism of heart failure (HF). Based on the CANTOS trial, interleukin-1β (IL-1β) inhibitor canakinumab reduces the heart failure-related mortality in subgroups with the concomitant elevation of infective adverse effects. These findings imply the need for more specific therapies. Inflammasomes, activators of the mature IL-1β, are intracellular danger signal sensing complexes. Based on our previous research, absent in melanoma 2 (AIM2) inflammasome protein showed elevated expression levels in left ventricular failure in rodents and humans. However, there is little data on how the expression patterns of inflammasome proteins change in decompensation of HF.
Aims: We aimed to investigate the expression patterns of inflammasome proteins in pressure-overload induced HF rodent model from the heart, the lungs, the liver and the kidneys.
Method: Transversal aortic constriction (TAC) was performed on rats, and impaired pump function was verified with echocardiography. According to a point scoring system based on clinical symptoms, the animals were classified into mild (TAC-M) and decompensated (TAC-HF) groups, then expression levels of inflammasome proteins [e.g. NLRP3 (NLR family domain containing 3), NLRC4 (NLR family containing a CARD 4)] were measured by Western blotting.
Results: Due to decompensation, the left and right ventricles featured elevated levels of AIM2 (p=0.0388; and p= 0.0018) and NLRC4 (p=0.0098; and p=0.0022), two sensor proteins. Decompensation lead to elevated levels of NLRP3 (p=0.0003), another sensor protein type in the lung. Liver tissue paradoxically featured reduced levels of inflammasome components, meanwhile the kidney featured no inflammasome-induced inflammation. In contrast to decompensation, mild HF groups were presented with less pronounced protein expression levels.
Conclusion: The role of inflammasomes in decompensation is more prominent in the heart and in the lung. These patterns imply the use of sensor proteins as specific drug targets and biomarkers in advanced HF.
RRF-2.3.1-21-2022-00003, TKP2021-EGA-23, European Union's Horizon 2020 Research and Innovation Programme (grant agreement no. 739593), Momentum Research Grant LP-2021-14 (to Z.V.V.), NKFIH K134939 (to T.R.) and FK134751 (to Z.V.V.), ÚNKP-22-3-I SE-7 (to D.N.), ÚNKP-23-4-II-SE-26 (to Zs.O.)