3,4-benzo[a]pyrene aggravates myocardial infarction injury by activating NLRP3-related pyroptosis through PINK1/Parkin-mitophagy-mPTP opening axis

Abstract Acute myocardial infarction(AMI) accounts for more than one third of ischemic heart disease deaths. Air pollution exposure,even for a short-term exposure,is conspicuously relevant to increased risk of MI mortality and clinical evidence has showed that air pollution particulate matter(PM) induces the aggravation of AMI.3,4-benzo[a]pyrene(BaP),a polycyclic aromatic hydrocarbon(PAH) with toxicity,is a typical air pollutant present in PM and is often measured as the representative of PAHs.The purpose of this study was to investigate whether BaP can aggravate myocardial infarction(MI) injury and,on this basis,to investigate the relevant mechanisms.The MI mouse model and the oxygen and glucose deprivation(OGD) H9C2 cell model were used to investigate the effect of BaP in MI injury.The involvement of mitophagy and NLRP3-related pyroptosis in regulating deterioration of cardiac function and aggravation of MI injury induced by BaP was comprehensively evaluated.Our study showed that BaP can aggravate MI injury in vivo and in vitro,and this result was based on NLRP3-related pyroptosis induced by BaP.In addition,BaP can inhibit PINK1/Parkin dependent mitophagy through the aryl hydrocarbon receptor(AhR),thus inducing mitochondrial permeability transition pore(mPTP) opening.Our results suggested a role for the BaP from air pollution in the aggravation of MI injury and revealed that BaP aggravates MI injury by activating NLRP3-related pyroptosis through PINK1/Parkin-mitophagy-mPTP opening axis.