Simvastatin Inhibits the Proliferation and Apoptosis of Macrophages Induced by Mechanical Stress and/or Oxidized Low-Density Lipoprotein

This study was designed to investigate the effects of mechanical stress (MS) and/or oxidized low-density lipoprotein (oxLDL) 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/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 an additive effect. In terms of mechanisms, MS and/or oxLDL significantly increased phosphorylation levels of MAPKs (ERKs, JNKs and p38MAPK), promoted the reactive oxygen species (ROS) and up-regulated DNA methylation in RAW264.7 macrophages. The increased DNA methylation was associated with Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510089, Guangdong, China. Department of Histology and Embryology, Xiangnan University, Chenzhou, 423000, Hunan Province, China. Guangzhou Institute of Cardiovascular Disease, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong, China Department of orthopedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510089, Guangdong, China. Medical Experimental Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510089, Guangdong, China. Correspondence should be addressed to Shuying Liu and Chaohong Li, Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, 74# Zhongshan Road 2, Guangzhou, 510089, Guangdong Province, China. Tel.: +86-(0)20-87332488;Fax: +86-(0)20-87331451;E-mail: liushuy3@mail.sysu.edu.cn and lichaoh@mail.sysu.edu.cn §These authors are equal contribution 102 Copyright © 2017 Tech Science Press MCB, vol.14, no.2, pp.101-123, 2017 proliferation but not apoptosis. In contrast, simvastatin could remarkably inhibit all the effects mentioned above. MS and oxLDL can simultaneously promote both proliferation and apoptosis of macrophages through activating MAPKs, ROS, and DNA methylation signaling, which can be directly inhibited by the simvastatin treatment. The study results can provide novel information for the pathogenesis and prevention of hypertensive mechanical stress-related vascular diseases. Short title: Proliferation and Apoptosis of Macrophages