PM2.5 Induces the Instability of Atherosclerotic Plaques by Activating the Notch Signaling Pathway In Vivo and In Vitro.

Abstract

Fine particulate matter (PM_2.5) can exacerbate the instability of atherosclerotic plaques although the exact chemical process driving atherosclerosis remains unknown. In order to create atherosclerotic models, a high-fat diet and vitamin D3 injections were given to 56 Wistar rats in this investigation. The atherosclerotic rats were split into four groups at random and given different doses of PM_2.5 (0, 1.5, 7.5, and 37.5 mg/kg) for 4 weeks. To investigate the mechanism, foam cells were exposed to PM_2.5 (0, 25, 50, and 100 μg/mL) for 24 h. The results showed that PM_2.5 exposure caused collagen fibers thinner and muscle fibers were disorganized. PM_2.5 exposure significantly affected the expression of MMP2, MMP9, TIMP2, and vimentin in aortas of atherosclerotic rats. Moreover, PM_2.5 exposure increased the expression of the Notch signaling pathways which was correlated with the expression of atherosclerotic plaque stability-related genes. PM_2.5 exposure also increased the apoptosis rate of foam cells. The expression of MMP2, MMP9, and vimentin was increased and TIMP2 was decreased with the increasing PM_2.5 dose in foam cells. The inhibition of the Notch signaling pathway can alleviate the alteration of atherosclerotic plaque stability-related genes. The findings demonstrated that PM_2.5 exposure can cause atherosclerotic plaques to become unstable, aggravating the progression of atherosclerosis, a process in which the Notch signaling pathway is crucial.