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

Background: Air pollution is an important and interventionable risk factor for cardiovascular disease. Air pollution exposure, even for a short-term exposure, is conspicuously relevant to increased risk of myocardial infarction (MI) mortality and clinical evidence has shown that air pollution particulate matter (PM) induces the aggravation of AMI. 3,4-benzo[a]pyrene (BaP), an extremely toxic polycyclic aromatic hydrocarbon (PAH) and a common component of PM, is listed as one of the main objects of environmental pollution monitoring. Both epidemiological and toxicological studies suggest that BaP exposure may be associated with cardiovascular disease. Since PM is significantly associated with the increased risk of MI mortality, and BaP is an important component of PM associated with cardiovascular disease, we intend to investigate the effect of BaP on MI models.
Methods: 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 pyroptosis in regulating deterioration of cardiac function and aggravation of MI injury induced by BaP was comprehensively evaluated.
Results: Our study shows that BaP exacerbates MI injury in vivo and in vitro, a result based on BaP-induced NLRP3-related pyroptosis. In addition, BaP can inhibit PINK1/Parkin dependent mitophagy through the aryl hydrocarbon receptor (AhR), thus the mitochondrial permeability transition pore (mPTP) was induced to open.
Conclusion: Our results suggest a role for the BaP from air pollution in MI injury aggravation and reveal that BaP aggravates MI injury by activating NLRP3-related pyroptosis via the PINK1/Parkin-mitophagy-mPTP opening axis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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