Silica nanoparticles promoted pro-inflammatory macrophage and foam cell transformation via ROS/PPAR7/NF-xB signaling

Experimental evidence has pointed out silica nanoparticles (SiNPs) possessing a proatherogenic capability. However, the interplay between SiNPs and macrophages in the pathogenesis of atherosclerosis was poorly understood. Here, we demonstrated SiNPs could promote macrophage adhesion to endothelial cells, accompanied by elevated Vcam1 and Mcp1. Upon SiNPs stimuli, macrophages manifested enhanced phagocytic activity and a pro-inflammatory phenotype, as reflected by the transcriptional determination of M1/M2-related biomarkers. In particular, our data certified the in-creased macrophage M1 subset facilitated more lipid accumulation and resultant foam cell transformation in compar-ison to the M2 phenotype. More importantly, the mechanistic investigations revealed ROS-mediated PPAR7/NF-xB signaling was a key contributor to the above phenomena. That was, SiNPs caused ROS accumulation in macrophages, resulting in the deactivation of PPAR7, nuclear translocation of NF-xB, ultimately contributing to macrophage pheno-type shift toward M1 and foam cell transformation. Collectively, we first revealed SiNPs facilitated pro-inflammatory macrophage and foam cell transformation via ROS/PPAR7/NF-xB signaling. These data would provide new insight into the atherogenic property of SiNPs in a macrophage model.