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

This study was designed to investigate the effects ofmechanical (MS)and/or oxidized low-density lipoprotein on proliferation and apoptosis of RAW264.7 macrophages and the underlying mechanisms. The cultured quiescent RAW264.7 macrophages were subject to stimulation with MS and/orin the presence or absence of simvastatin and then harvested for Western blot, and immunoflourecence. Either MS oralone could cause increase incell proliferation and apoptosis, while their combination led to anadditiveeffect. In terms of mechanisms, MS and/or significantly increased phosphorylation levels of MAPKs (ERKs, JNKs and p38MAPK), promoted the reactive oxygen species (ROS) and up-regulated DNA methylationin RAW264.7 macrophages. The increased DNA methylation was associated with proliferation but not apoptosis. In contrast, simvastatin could remarkably inhibit all the effects mentioned above. MS and can simultaneously promote both proliferation and apoptosis of macrophages through activating MAPKs, ROS, and DNA methylation signaling, which can be directly in hibited by the simvastatin treatment. The study results can provide novel information for the pathogenesis and prevention of hypertensive mechanical related vascular diseases.