Carbonaceous cores serve as surrogates for environmental particulate matter inducing vascular endothelial inflammation via inflammasome activation

Abstract

Ambient particulate matter (PM) exposure is a known risk factor for cardiovascular diseases. Epidemiological studies have shown the association between PM exposure and vascular complications, including vasculitis, embolism, hypertension, stroke, and atherosclerosis. However, the exact mechanisms underlying its vascular toxicity, especially in relation to short-term exposures, remain incompletely understood. This study investigates the role of PM and its carbonaceous cores in driving vascular endothelial inflammation via inflammasome activation. We hypothesized that PM SRM1648a exposure induces vascular endothelial inflammation through oxidative stress and inflammasome activation. Short-term exposure to PM SRM1648a was assessed in BALB/c mice for systemic inflammation and oxidative stress biomarkers, alongside in vitro studies in HUVECs and EA.hy926 endothelial cells to elucidate inflammasome activation pathways. PM SRM1648a exposure significantly altered redox balance and cytokine profiles in mice and upregulated NLRP3/NLRC4 inflammasomes in vascular endothelial cells, leading to caspase-1/IL-1β activation. Intriguingly, pyroptosis was not the primary mode of cell death. In vitro studies demonstrated that antioxidants glutathione monoethyl ester effectively mitigated oxidative stress and inflammasome activation in endothelial cells. This study highlights the critical role of ROS-mediated inflammasome activation in vascular inflammation induced by PM SRM1648a, with carbon-based cores as key contributors.

Keywords: Carbon black; Caspase; Endothelial cell; Inflammasome; PM2.5; Pyroptosis.