Cardiovascular disease is a common comorbidity in patients with cancer,and the main leading cause of noncancer-related deaths in cancer survivors.Considering that current antitumor drugs usually induce cardiovascular injury,the quest for developing new antitumor drugs,especially those with cardiovascular protection,is crucial for improving cancer prognosis.MK2206 is a phase Ⅱclinical anticancer drug and the role of this drug in cardiovascular disease is still unclear.Here,we revealed that MK2206 significantly reduced vascular inflammation,atherosclerotic lesions,and inhibited proliferation of vascular smooth muscle cell in ApoE-/-mice in vivo.We demonstrated that MK2206 reduced lipid accumulation by promoting cholesterol efflux but did not affect lipid uptake and decreased inflammatory response by modulating inflammation-related mRNA stability in macrophages.In addition,we revealed that MK2206 suppressed migration,proliferation,and inflammation in vascular smooth muscle cells.Moreover,MK2206 inhibited proliferation and inflammation of endothelial cells.The present results suggest that MK2206,as a promising drug in clinical antitumor therapy,exhibits anti-inflammatory and antiatherosclerotic potential.This report provides a novel strategy for the prevention of cardiovascular comorbidities in cancer survivors.

Ya-qin Tang;Zhi-wei Li;Yu-fan Feng;Hong-qin Yang;Cui-liu Hou;Chi Geng;Pei-ran Yang;Hong-mei Zhao;Jing Wang

State Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Department of Pathophysiology,Peking Union Medical College,Beijing 100005,China

中国药理学报（英文版）

[1]Ya-qin Tang;Zhi-wei Li;Yu-fan Feng;Hong-qin Yang;Cui-liu Hou;Chi Geng;Pei-ran Yang;Hong-mei Zhao;Jing Wang-.MK2206 attenuates atherosclerosis by inhibiting lipid accumulation,cell migration,proliferation,and inflammation)[J].中国药理学报（英文版）,2022(04):897-907

noncancer,antiatherosclerotic

MK2206,attenuates,atherosclerosis,by,inhibiting,lipid,accumulation,migration,proliferation,inflammation,Cardiovascular,disease,common,comorbidity,patients,main,leading,cause,related,deaths,survivors,Considering,that,current,antitumor,drugs,usually,induce,cardiovascular,injury,quest,developing,new,especially,those,protection,crucial,improving,prognosis,phase,clinical,anticancer,role,this,still,unclear,Here,we,revealed,significantly,reduced,lesions,inhibited,smooth,muscle,ApoE,mice,We,demonstrated,promoting,cholesterol,efflux,but,did,not,affect,uptake,decreased,inflammatory,response,modulating,stability,macrophages,In,addition,suppressed,cells,Moreover,endothelial,present,results,suggest,promising,therapy,exhibits,potential,This,report,provides,novel,strategy,prevention,comorbidities

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