Exposure to polyethylene terephthalate micro(nano)plastics exacerbates inflammation and fibrosis after myocardial infarction by reprogramming the gut and lung microbiota and metabolome

Micro(nano)plastics (MNPs), a ubiquitous environmental pollutant, have received increasing attention for their impacts on human health. We conducted an in-depth study on the role of polyethylene terephthalate (PET) MNPs in myocardial infarction (MI). Blood from the coronary circulation of MI patients was collected to detect microplastics (MPs). Peripheral monocytes (PBMCs) and AC16 cells were used to assess inflammation, cell proliferation and apoptosis after PET nanoplastics (NPs) stimulation. The mouse MI model was established after PET NPs respiratory or oral exposure. The results showed that various types of MPs, including high levels of PET MPs, were detected in the coronary circulation. PET NPs promoted inflammatory factors secretion by PBMCs, inhibited AC16 cell proliferation and promoted hypoxia-induced AC16 cell apoptosis. PET NPs exacerbated post-MI inflammation and fibrosis through activating the NLRP3 inflammasome pathway. Through macrogenetic sequencing and metabolomics analyses, we observed that PET NPs reprogrammed the intestinal and lung microbiota and metabolome in MI mice, leading to chronic inflammation. In conclusion, PET MPs were widely present in the coronary circulation of MI patients. PET MNPs can activate the NLRP3 inflammasome pathway to exacerbate post-MI ventricular remodelling, which may be related to the reprogramming of the gut and lung microbiota and metabolome.