Objective::The effectiveness of statins in reducing atherosclerotic calcification remains controversial. The aim of this study was to confirm that simvastatin reduces atherosclerotic calcification and stabilizes plaque by restricting endoplasmic reticulum stress (ERS)-mediated apoptosis.Methods::Twenty-four 8-week-old male apolipoprotein E (ApoE) -/- mice (C57BL/6J genetic background) were selected and randomly divided into model ( n = 12) and simvastatin ( n = 12) groups. Twelve male C57BL/6J mice were selected as control group ( n = 12). The mice were adaptively fed for 2 weeks and were put on a high-fat diet thereafter. After 9 weeks, they were treated with simvastatin (20 mg/kg) or phosphate-buffered saline daily for 8 weeks. Aortic sinus samples were obtained from ApoE -/- and C57BL/6J mice for hematoxylin and eosin, von Kossa, alizarin Red S, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and immunohistochemical staining after in vivo treatment with simvastatin. In addition, mouse vascular smooth muscle cells were analyzed after exposure to simvastatin in vitro.Results::Administration of simvastatin in vivo drastically attenuated the atherosclerosis, calcification, and apoptosis, and decreased the serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The expression levels of glucose-regulated protein, 78 kDa (GRP78), C/EBP homologous protein (CHOP), and caspase 12 (CASP12) in the aortic sinus decreased in the simvastatin group compared with the model group. In vitro, simvastatin or simvastatin plus ERS inhibitor (taurine) attenuated calcification and apoptosis, and reduced the expression of ERS-related proteins GRP78, CHOP, and CASP12. Conclusion::Treatment with simvastatin suppressed atherosclerotic calcification. This effect may be mediated through the inhibition of ERS-related apoptosis.

Endoplasmic reticulum stress;Statins;Atherosclerotic calcification;Apoptosis

Li Jianhua;Zhao Libo;Zhou Zhe;Liu Lin;Zou Xiao;Xu Weihao;Fan Li;Yan Muyang;Wang Shengqi

Cardiology Department of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army General Hospital, Beijing 100853, China;Graduate School of Medical School of Chinese People.s Liberation Army, Beijing 100853, China;Beijing Institute of Radiation Medicine, Beijing 100850, China;Department of Respiratory and Critical Care Medicine of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People s Liberation Army General Hospital, Beijing 100093, China;Department of Hyperbaric Oxygen & Institute of Geriatric Cardiovascular Disease, Chinese People s Liberation Army General Hospital, Beijing 100093, China

心血管病探索（英文）

[1]Li Jianhua;Zhao Libo;Zhou Zhe;Liu Lin;Zou Xiao;Xu Weihao;Fan Li;Yan Muyang;Wang Shengqi-.Effects of Simvastatin on Endoplasmic Reticulum Stress-Mediated Apoptosis in Atherosclerotic Calcification)[J].心血管病探索（英文）,2022(04):209-217

Calcification,ApoE ,CASP12,Statins

Effects,Simvastatin,Endoplasmic,Reticulum,Stress,Mediated,Apoptosis,Atherosclerotic,Objective,effectiveness,statins,reducing,atherosclerotic,calcification,remains,controversial,aim,this,study,was,confirm,that,simvastatin,reduces,stabilizes,plaque,by,restricting,endoplasmic,reticulum,stress,ERS,mediated,apoptosis,Methods,Twenty,four,old,male,apolipoprotein,mice,C57BL,6J,genetic,background,were,selected,randomly,divided,into,model,groups,Twelve,control,adaptively,fed,weeks,put,high,fat,diet,thereafter,After,they,treated,phosphate,buffered,saline,daily,Aortic,sinus,samples,obtained,from,hematoxylin,eosin,von,Kossa,alizarin,Red,terminal,deoxynucleotidyl,transferase,dUTP,nick,labeling,immunohistochemical,staining,vivo,treatment,In,addition,mouse,vascular,smooth,muscle,cells,analyzed,exposure,vitro,Results,Administration,drastically,attenuated,atherosclerosis,decreased,serum,levels,triglycerides,total,cholesterol,low,density,expression,glucose,regulated,kDa,GRP78,EBP,homologous,CHOP,caspase,aortic,compared,plus,inhibitor,taurine,reduced,related,proteins,Conclusion,Treatment,suppressed,This,may,through,inhibition

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