Fine particulate matter induces cardiac fibrosis via the CHOP/TXNIP/NLRP3 pathway in C57 BL/6 mice.

Fine particulate matter (PM2.5) exposure can cause cardiovascular diseases (CVD) through cardiac fibrosis, but the underlying mechanisms driving this association are still unclear. Given the importance of endoplasmic reticulum stress (ERS), TXNIP, and pyroptosis in PM2.5-induced organ damage, we subsequently investigated their roles in PM2.5-induced cardiac fibrosis. To investigate the impact of PM2.5 on cardiac fibrosis in SPF C57BL/6 mice, we performed histopathology analysis on heart tissue exposed to varying PM2.5 dosages. Real-time PCR, commercial kits, and Western blotting are also being used to assess the degree of cardiac fibrosis in groups. In addition, the cardiac activation of the ERS/TXNIP/NLRP3 signaling pathway is examined. Significant fibrosis was observed in the heart tissue of mice that were exposed to high PM2.5 concentrations. The expression of key fibrosis markers and mediators was elevated, including α-SMA, CTGF, FN, and TGF-β1, along with the accumulation of ECM components (COL-I and COL-III). Compared to the control group, the PM2.5 was more intense, and Bip, PERK, p-PERK, CHOP, TXNIP, and ERS in the heart were all activated. Our findings demonstrate that PM2.5 exposure causes ERS and activates TXNIP in mice heart tissue. Further, the PM2.5 groups showed the raised expression of caspase-1, NLRP3, TXNIP, GSDMD-N, CRT, Caspase-3, and caspase-9. Our findings suggest that PM2.5 causes cardiac fibrosis by activating ERS, via TXNIP, inducing the activation of pyroptosis and apoptosis. The findings provide evidence that PM2.5-induced cardiac fibrosis through ERS-mediated activation of the CHOP/TXNIP/NLRP3 pathway, and provide insights into the underlying mechanisms of PM2.5-induced cardiac fibrosis.