Open Access

ARTICLE

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

Kefeng Liu^{1,2, §}, Zhengyu Zhang^{1,3, §}, Ting Pei¹, Ziqing Li⁴, Jingjing Wang¹, Hong Wang¹, Suning Ping¹, Lie Deng¹, Linli Wang¹, Jintao Huang⁵, Puyi Sheng⁴, Shuying Liu¹, Chaohong Li¹

1 Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat -sen University, Guangzhou, 510089, Guangdong, China.
2 Department of Histology and Embryology, Xiangnan University, Chenzhou, 423000, Hunan Province, China.
3 Guangzhou Institute of Cardiovascular Disease, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong, China
4 Department of orthopedic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510089, Guangdong, China.
5 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

Molecular & Cellular Biomechanics 2017, 14(2), 101-123. https://doi.org/10.3970/mcb.2017.014.099

Abstract

This study was designed to investigate the effects of mechanical (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/or in the presence or absence of simvastatin and then harvested for Western blot, and immunoflourecence. Either MS or alone could cause increase in cell proliferation and apoptosis, while their combination led to an additive effect. 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 methylation in 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 inhibited by the simvastatin treatment. The study results can provide novel information for the pathogenesis and prevention of hypertensive mechanical related vascular diseases.

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