Fine particulate matter-induced cardiovascular injury is associated with NLRP3 inflammasome activation in Apo E-/- mice.

Epidemiological evidences have indicated that fine particulate matter (PM2.5) is associated with the increased risk of cardiovascular morbidity and mortality. Although several mechanisms linking PM2.5 and inflammatory responses have been widely implicated, the detailed mechanisms involving the occurrence of inflammation in PM2.5-induced adverse effects are lacking. This study aims to investigate whether PM2.5 exposure-induced cardiovascular injury is associated with NLRP3 inflammasome activation in apolipoprotein E-/- (Apo E-/-) mice. Thirty-two Apo E-/- mice were randomly divided into four groups. The mice were fed with normal chow (NC) or high-fat chow (HFC) for 10 weeks, respectively. From week 11, the mice were exposed to concentrated PM2.5 (PM) or filter air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. The cardiac function and myocardial injury were evaluated by echocardiography and histopathological examination. Meanwhile, the expression of NLRP3-related signaling pathway in myocardium was detected. Compared with the FA mice, the PM mice showed the underlying cardiac dysfunction and injury in both NC and HFC groups. Mononuclear macrophages (CD11c+) were significant higher in bone marrow of the PM mice than that in the FA mice, whilst CD206+ macrophages were lower. Accordingly, PM2.5 exposure induced the increase of circulating inflammatory cytokine TNF-α and decrease of anti-inflammatory cytokine IL-10. PM2.5 exposure was also associated with the activation of NLRP3 inflammasome, which characterized by elevated protein expression of NLRP3, ASC, caspase-1, IL-1β and IL-18 in myocardium. All these results demonstrated PM2.5-related cardiac injury is mediated by macrophages polarization and NLRP3 inflammasome activation.