Neutralization of IL ‐ 17A Ameliorates PM2.5‐Induced Cardiac Inflammation and Fibrosis in Rats by Suppressing the TXNIP / NLRP3 Signaling Pathway

ABSTRACT Fine particulate matter (PM2.5) pollution is a major environmental risk factor for cardiovascular diseases. Exposure can cause cardiac inflammation and fibrosis. However, whether interleukin‐17A (IL‐17A) contributes to these effects is unclear. Here, a rat cardiac injury model was established by intratracheal instillation of PM2.5, and an IL‐17A neutralizing antibody was administered. PM2.5 exposure increased the proportion of splenic CD4 + IL‐17A + T cells and IL‐17A/TRAF6 expression in cardiac tissue, with impaired cardiac function, myocardial inflammatory infiltration, collagen deposition, and increased expression of α‐SMA and Collagen I/III. Cardiac tissue exhibited increased oxidative stress, enhanced NF‐κB activation, elevated IL‐6 and IL‐1β, upregulated TXNIP, and activation of the NLRP3 inflammasome and pyroptosis‐related proteins (ASC, cleaved Caspase‐1 p20, GSDMD‐N, and IL‐18). Neutralizing IL‐17A reversed these abnormalities and improved cardiac function. In vitro, IL‐17A upregulated TXNIP/NLRP3 and increased the expression of inflammatory cytokines and extracellular matrix components in neonatal rat cardiac fibroblasts (NRCFs), whereas TXNIP knockdown reversed these effects. These results identify IL‐17A as a key driver of PM2.5‐induced cardiac inflammation and fibrosis, and targeting the IL‐17A–TXNIP/NLRP3 axis may offer a new approach to treating PM2.5‐related cardiac injury.