Simvastatin inhibits the proliferation and apoptosis of macrophages induced bymechanical stress and/or oxidized low-density lipoprotein

This study was designed to investigate the effects ofmechanical stress (MS)and/or oxidized low-density lipoprotein (oxLDL) on proliferation and apoptosis ofRAW264.7 macrophages and the underlying mechanisms. The cultured quiescent RAW264.7 macrophages were subject to stimulation withMS and/or oxLDL in the presence or absence of simvastatin and then harvested for Western blot, and immunoflourecence.Either MS or oxLDL alone could cause increase in cell proliferation and apoptosis, while their combination led to anadditiveeffect. In terms of mechanisms, MS and/or oxLDL significantly increasedphosphorylation levels of MAPKs (ERKs, JNKs and p38MAPK), promotedthe reactive oxygen species (ROS) and up-regulatedDNA methylationin RAW264.7 macrophages.The increasedDNA methylationwas associated with proliferationbutnot apoptosis.In contrast, simvastatin could remarkably inhibit all the effectsmentioned above. MS and oxLDL can simultaneously promote both proliferation and apoptosis ofmacrophagesthrough activating MAPKs, ROS, and DNA methylation signaling,which can be directly inhibitedby the simvastatin treatment. The study results can provide novel informationfor the pathogenesis and prevention of hypertensive mechanical stress-related vascular diseases.