Multiorgan characterization of inflammasome component expression in a rat model of advanced heart failure

Nagy, Dávid and Onódi, Zsófia and Kocsis, Márton and Tóth, Artúr and Bálint, Tímea and Oláh, Attila and Sayour, Alex Ali and Barta, Bálint András and Merkely, Béla and Ferdinandy, Péter and Radovits, Tamás and Varga V., Zoltán and Ruppert, Mihály (2025) Multiorgan characterization of inflammasome component expression in a rat model of advanced heart failure. ESC Heart Failure, 12 (5). pp. 3601-3613. ISSN 2055-5822

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Abstract

Aims: Targeting inflammasomes in heart failure (HF) might represent a novel therapeutic option. Nevertheless, previous studies focused only on myocardial inflammasome alterations, and data are scarce regarding their regulation and role in HF-associated multiorgan dysfunction. Therefore, we aimed to determine the myocardial, pulmonary, hepatic and renal expression of various inflammasome components in a rat model of advanced HF. Methods and results: Rats underwent transverse aortic constriction (TAC) and were followed-up for 15 weeks. Animals featuring two to three clinical signs of advanced HF were included in the TAC-HF group (n = 6). TAC rats with mild HF were also investigated (0-1 signs, TAC-M group, n = 6). Six sham-operated animals served as controls. The expressions of inflammasome component proteins in left ventricle (LV), right ventricle (RV), lung, liver and kidney tissue were measured with Western blot. Despite the differences between the clinical state of the TAC-HF and TAC-M groups, severe cardiac dysfunction and myocardial remodelling developed in all TAC animals. Absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasome sensors were up-regulated in both the LV and RV of the TAC-HF group compared with sham. AIM2 and NLR family pyrin domain-containing protein 3 (NLRP3), but not NLRC4 expression were elevated in the lungs of the TAC-HF animals. Additionally, pulmonary congestion and CD68-positive leukocyte infiltration were observed in both TAC groups. Inflammasome components were down-regulated in the liver and remained unchanged in the kidneys of the TAC-HF group, despite the presence of renal atrophy and fibrosis. Inflammasome changes were predominantly absent in TAC-M animals. Conclusions: Inflammasome expression shows distinct patterns in specific organs in advanced HF. Future studies aiming to antagonize inflammation in HF should take these findings into consideration.

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