Pyroptosis results in activation of the NLRP3 inflammasome, which leads to the caspase-1-dependent release of IL-1β and GSDMD-mediated pyroptotic cell death.44 Here, we show that activation of NLRP3 is involved in ACSL4-induced cardiac dysfunction during TAC-induced pressure overload, with activation of caspase-1, cleavage of IL-1β and GSDMD, and induction of cardiomyocyte death. The gene discussed is ACSL4; the disease is persistent truncus arteriosus.