Intestinal barrier damage is associated with fine particulate matter (PM2.5)-induced pathological aortic injury in mice.

Abstract

Chronic exposure to air pollution is associated with an increased cardiovascular disease (CVD) risk, and inflammation induced by fine particulate matter (PM2.5) exposure is a key driver in CVD development. However, the mechanism by which PM2.5 causes cardiacovescular damage remains unclear. Here, Balb/c mice were intratracheally instilled with PM2.5 suspension at doses of 2.0 mg/kg or 4.0 mg/kg body weight for 7 consecutive days to establish an aortic injury model. Pathological changes were assessed by hematoxylin and eosin (H&E), elastic Van Gieson, and Masson's trichrome staining. Potential pathways were identified through GeneCards database analysis, R language, and Metascape pathway enrichment analysis. Immune cell profiles in the blood were analyzed by flow cytometry, and serum inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Confocal microscopy was used to evaluate inflammatory cell infiltration in the aorta. Intestinal barrier integrity was assessed by transmission electron microscopy; H&E, and immunofluorescence staining; and western blotting. We found that high-dose PM2.5 exposure led to inflammatory cell infiltration, disorganization of elastic fiber layers, and aortic tissue fibrosis. Pathway enrichment analyses indicated the involvement of pathways related to the regulation of inflammatory responses and responses to bacterial molecules. Increased inflammatory cells and pro-inflammatory cytokines were detected in the blood, accompanied by an increase in circulating lipopolysaccharide. PM2.5 exposure disrupted the intestinal mucosal barrier, leading to reduced claudin-1 and occludin (tight junction protein) expression, which exacerbated systemic inflammation and induced aortic injury. In conclusion, PM2.5 exposure caused pathological aortic damage and exacerbated systemic inflammation, potentially mediated by compromised intestinal barrier integrity.