Translational Medicine - Posters O
Dávid Nagy1, Zsófia Gulyás-Onódi2, Tímea Bálint1, Alex Ali Sayour1, Attila Oláh1, Bálint András Barta1, Péter Ferdinandy2, Béla Merkely1, Zoltán Varga2, Tamás Radovits1, Mihály Ruppert1
1 Heart and Vascular Centre, Semmelweis University, Budapest
2 Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest
Introduction: The consequences of heart failure (HF) pose a significant challenge for healthcare systems worldwide. Inflammatory mediators, such as interleukin-1β (IL-1β) are known to be involved in the pathophysiology and prognosis of HF. The production of IL-1β is regulated by multiprotein complexes i.e. inflammasomes. Recent research has demonstrated that inflammasomes are involved in various types of HF. However, there is no comprehensive study yet that investigates the inflammasomal expression patterns in right ventricular (RV) HF induced by left ventricular (LV) dysfunction.
Aims: Hence, the goal of this experiment was to characterize the expression levels of various inflammasome components in a small animal model of LV HF associated with RV dysfunction as well.
Method: Transverse aortic constriction (TAC) was performed in young male Wistar rats to induce chronic hemodynamic overload of the LV, resulting in LV HF eventually. A fraction of these animals also presented clinical signs of RV HF such as peripheral edema and tachypnea. We formed our RV HF study group from these rapidly decompensating animals. Sham-operated rats served as controls. We measured the expression levels of various inflammasome markers in the LV, RV and lung tissue using Western blot analysis.
Results: The myocardial expressions of inflammasome markers showed an overall increasing tendency in the TAC animals. NLRC4 (NLR family CARD domain containing protein 4), AIM2 (absent in melanoma 2) and gasdermin D were found to be overexpressed in the failing RV. IL-1β levels elevated in both ventricles. In lung tissue however, the NLRP3 (NLR family pyrin domain containing 3), AIM2 and IL-1β expressions increased, while NLRC4 and gasdermin D showed no significant difference compared with the controls.
Conclusion: LV dysfunction coupled with RV HF is associated with inflammasome priming, indicated by the elevated expression levels of inflammasome components. In the LV, RV and lung tissues however, different markers were found to be overexpressed. Future studies, especially on serum samples might prove the feasibility of using the inflammasomes as prognostic markers of the progression of HF.
Funding: NKFIH K134939 (to T.R.); TKP2021-EGA-23; RRF-2.3.1-21-2022-00003_NKL_VMKL; ÚNKP-22-3-I (to D.N.)