典型文献
Dapagliflozin attenuates pressure overload-induced myocardial remodeling in mice via activating SIRT1 and inhibiting endoplasmic reticulum stress
文献摘要：
Endoplasmic reticulum stress-mediated apoptosis plays a vital role in the occurrence and development of heart failure.Dapagliflozin(DAPA),a new type of sodium-glucose cotransporter 2(SGLT2)inhibitor,is an oral hypoglycemic drug that reduces glucose reabsorption by the kidneys and increases glucose excretion in the urine.Studies have shown that DAPA may have the potential to treat heart failure in addition to controlling blood sugar.This study explored the effect of DAPA on endoplasmic reticulum stress-related apoptosis caused by heart failure.In vitro,we found that DAPA inhibited the expression of cleaved caspase 3,Bax,C/EBP homologous protein(CHOP),and glucose-regulated protein78(GRP78)and upregulated the cardiomyoprotective protein Bcl-2 in angiotensin Ⅱ(Ang Ⅱ)-treated cardiomyocytes.In addition,DAPA promoted the expression of silent information regulator factor 2-related enzyme 1(SIRT1)and suppressed the expression of activating transcription factor 4(ATF4)and the ratios p-PERK/PERK and p-eIF2α/eIF2α.Notably,the therapeutic effect of DAPA was weakened by pretreatment with the SIRT1 inhibitor EX527(10 μM).Simultaneous administration of DAPA inhibited the Ang Ⅱ-induced transformation of fibroblasts into myofibroblasts and inhibited fibroblast migration.In summary,our present findings first indicate that DAPA could inhibit the PERK-eIF2α-CHOP axis of the ER stress response through the activation of SIRT1 in Ang Ⅱ-treated cardiomyocytes and ameliorate heart failure development in vivo.
文献关键词：
中图分类号：
作者姓名：
Fang-fang Ren;Zuo-yi Xie;Yi-na Jiang;Xuan Guan;Qiao-ying Chen;Teng-fang Lai;Lei Li
作者机构：
Department of Cardiology,Institute of Cardiovascular Development and Translational Medicine,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325027,China;Department of Cardiology,The Affiliated Hospital of Youjiang Medical University for Nationalities,Baise 533000,China
文献出处：
引用格式：
[1]Fang-fang Ren;Zuo-yi Xie;Yi-na Jiang;Xuan Guan;Qiao-ying Chen;Teng-fang Lai;Lei Li-.Dapagliflozin attenuates pressure overload-induced myocardial remodeling in mice via activating SIRT1 and inhibiting endoplasmic reticulum stress)[J].中国药理学报（英文版）,2022(07):1721-1732
A类：
Dapagliflozin,DAPA,protein78,cardiomyoprotective
B类：
attenuates,pressure,overload,induced,myocardial,remodeling,mice,via,activating,SIRT1,inhibiting,endoplasmic,reticulum,stress,Endoplasmic,mediated,apoptosis,plays,vital,role,occurrence,development,heart,failure,new,type,sodium,glucose,cotransporter,SGLT2,inhibitor,oral,hypoglycemic,drug,that,reduces,reabsorption,by,kidneys,increases,excretion,urine,Studies,have,shown,may,potential,addition,controlling,blood,sugar,This,study,explored,effect,related,caused,In,vitro,found,inhibited,expression,cleaved,caspase,Bax,EBP,homologous,CHOP,GRP78,upregulated,Bcl,angiotensin,Ang,treated,cardiomyocytes,promoted,silent,information,regulator,enzyme,suppressed,transcription,ATF4,ratios,PERK,eIF2,Notably,therapeutic,was,weakened,pretreatment,EX527,Simultaneous,administration,transformation,into,myofibroblasts,migration,summary,our,present,findings,first,indicate,could,axis,response,through,activation,ameliorate,vivo
AB值：
0.533007
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