3,4-benzopyrene aggravates myocardial ischemia–reperfusion injury-induced pyroptosis through inhibition of autophagy-dependent NLRP3 degradation

Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[a]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia–reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation–reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53–BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53–BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated. Possible mechanism of pyroptosis and autophagy mediated by BaP during myocardial ischemia/reperfusion injury. Bap activated AhR translocate into cells and activates downstream p53. As a result, BaP is capable of enhancing the interaction between BNIP3 and Bcl-2 to mediate more “free” Beclin-1 to inhibit autophagosome processing. Ultimately, blockage of autophagy-dependent NLRP3 degradation was shown to aggravate cell pyroptosis during myocardial I/R injury. [Display omitted] •BaP induces potent cardiotoxic effect during myocardial I/R injury.•Bap aggravates pyroptosis in a mechanism of impaired autophagosome clearance.•Bap inhibited autophagosome clearance through Ahr-p53-BNIP3-Beclin-1 axis.