Exosomal microRNA-16-5p from macrophage exacerbates atherosclerosis via modulating mothers against decapentaplegic homolog 7

Studies have probed the function of microRNA (miR)-16-5p in the progression of atherosclerosis (AS), while the regulatory function of exosomal miR-16-5p from macrophage on AS remains largely unknown. This study commits to exploring the efficiency of exosomal miR-16-5p from macrophage on AS via modulating mothers against decapentaplegic homolog 7 (SMAD7). Macrophages were cultured and transfected with miR-16-5p antagomir, then, the exosomes from macrophages were extracted. The AS mouse model was established, and miR-16-5p or SMAD7 expression in AS mice was detected. Thereafter, the effects of macrophage-derived exosomes, miR-16-5p or SMAD7 on serum inflammatory response, oxidative stress response, pathological changes and apoptosis in AS mice were observed by immunohistochemical and biochemical analysis. Finally, the binding relation between miR-16-5p and SMAD7 was examined. MiR-16-5p was elevated while SMAD7 was depleted in AS mice. Macrophage-derived exosomes aggravated AS progression via facilitating inflammatory response and oxidative stress, exacerbating pathological changes and increasing cell apoptosis in AS mice; while downregulation of miR-16-5p reversed the exacerbation of AS progression by macrophage-derived exosomes in AS mice. MiR-16-5p targeted SMAD7, and the down-regulated SMAD7 reversed the impacts of depleted miR-16-5p on AS progression. Exosomal miR-16-5p from macrophages aggravates AS progression via downregulating SMAD7 expression. This study provides novel therapeutic targets for AS treatment from the animal level. •Macrophage-derived exosomes aggravate AS progression.•MiR-16-5p is up-regulated while SMAD7 is down-regulated in AS mice.•Silencing miR-16-5p or elevated SMAD7 improves AS progression.•SMAD7 deletion reverses the ameliorative effect of reduced miR-16-5p on AS development.•Decreased exosomal miR-16-5p from macrophage relieves AS via targeting SMAD7.