Abstract Background 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 advanced HF-associated multiorgan dysfunction. Purpose Therefore, we aimed to determine the myocardial, pulmonary, hepatic and renal expression of various inflammasome components in a surgical rat model of advanced HF. Methods Rats underwent transverse aortic constriction (TAC) surgery and were followed for 15 weeks. Using a simple scoring method, animals displaying 2-3 clinical signs of advanced HF were included in the TAC-HF group. TAC rats with mild HF were also investigated (0-1 signs, TAC-M group). 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. Results Despite the differences between the clinical state of the TAC-HF and TAC-M groups, severe cardiac dysfunction of comparable degree developed in all TAC animals. Absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) inflammasome sensors were upregulated in both the LV and RV of the TAC-HF group compared to 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. Inflammasome components were downregulated in the liver and unchanged in kidney tissue in the TAC-HF group. Inflammasome changes were predominantly absent in TAC-M animals. Conclusion Inflammasome expression shows distinct patterns in specific organs in advanced HF.
Horvath et al. (Fri,) studied this question.