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 auto-phagy 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.

Automated summary

Polycyclic aromatic hydrocarbons (PAHs) are widely present in the environment and are produced during combustion of organic matter. This study investigated the effect of 3,4-benzo[a]pyrene (BaP), a commonly studied PAH, on myocardial ischemia-reperfusion (I/R) injury. The results showed that BaP aggravated myocardial pyroptosis in an autophagy-dependent manner and activated the p53-BNIP3 pathway to decrease autophagosome clearance. These findings provide new insights into the mechanisms of cardiotoxicity and suggest the p53-BNIP3 pathway as a potential therapeutic target for BaP-induced myocardial I/R injury.