PM2.5 induce myocardial injury in hyperlipidemic mice through ROS-pyroptosis signaling pathway.

Exposure to particulate matters with diameters below 2.5 µm (PM2.5) is considered a major risk factor for cardiovascular diseases (CVDs). The closest associations between PM2.5 and CVDs have been observed in hyperbetalipoproteinemia cases, although the detailed underpinning mechanism remains undefined. In this work, hyperlipidemic mice and H9C2 cells were used to examine the effects of PM2.5 on myocardial injury and their underlying mechanisms. The results revealed that PM2.5 exposure caused severe myocardial damage in the high-fat mouse model. Oxidative stress and pyroptosis were also observed along with myocardial injury. After inhibiting pyroptosis with disulfiram (DSF), the level of pyroptosis was effectively reduced as well as myocardial injury, suggesting that PM2.5 induced the pyroptosis pathway and further caused myocardial injury and cell death. Afterwards, by suppressing PM2.5-induced oxidative stress with N-acetyl-L-cysteine (NAC), myocardial injury was markedly ameliorated, and the upregulation of pyroptosis markers was reversed, which indicated that PM2.5-pyroptosis was also improved. Taken together, this study revealed that PM2.5 induce myocardial injury through the ROS-pyroptosis signaling pathway in hyperlipidemia mice models, providing a potential approach for clinical interventions.