典型文献
Activation of the endocannabinoid system mediates cardiac hypertrophy induced by rosiglitazone
文献摘要：
Rosiglitazone(RSG)is a synthetic agonist of peroxisome proliferator-activated receptor-y(PPARy),which plays a central role in the regulation of metabolism.Meta-analyses have suggested that RSG is associated with increased cardiovascular risk.However,the mechanisms underlying such adverse cardiac effects are still poorly understood.Here,we found that activation of PPARy by RSG stimulated the endocannabinoid system(ECS),a membrane lipid signaling system,which induced cardiac hypertrophy.In neonatal rat cardiomyocytes,RSG increased the level of anandamide(AEA);upregulated the expression of N-acyl phosphatidylethanolamine phospholipase D(NapePLD),a key enzyme for AEA synthesis;and downregulated the expression of fatty acid amide hydrolase(FAAH),the enzyme responsible for the degradation of AEA.Importantly,PPARy activation increased the expression of cannabinoid receptor type 1(CB1)through an identified binding site for PPARy in the CB1 promoter region.Moreover,both the in vitro and in vivo results showed that inhibition of the ECS by rimonabant,an antagonist of CB1,attenuated RSG-induced cardiac hypertrophy,as indicated by decreased expression of cardiac hypertrophy markers(ANP and BNP),deactivation of the mTOR pathway,and decreased cardiomyocyte size.Thus,these results demonstrated that the ECS functions as a novel target of PPARy and that the AEA/CB1/mTOR axis mediates RSG-induced cardiac remodeling.
文献关键词：
中图分类号：
作者姓名：
Ya-han Liu;Yan Liu;Xu Zhang;Li Fang;Bei-lei Zhao;Nan-ping Wang
作者机构：
Key Laboratory of Molecular Cardiovascular Science,Ministry of Education●Institute of Cardiovascular Sciences,Peking University Health Science Center,Beijing 100191,China;Tianjin Key Laboratory of Metabolic Diseases,Department of Physiology and Pathophysiology,Tianjin Medical University,Tianjin 300070,China;East China Normal University Health Science Center,Shanghai 200241,China
文献出处：
引用格式：
[1]Ya-han Liu;Yan Liu;Xu Zhang;Li Fang;Bei-lei Zhao;Nan-ping Wang-.Activation of the endocannabinoid system mediates cardiac hypertrophy induced by rosiglitazone)[J].中国药理学报（英文版）,2022(09):2302-2312
A类：
rosiglitazone,anandamide,NapePLD,rimonabant
B类：
Activation,endocannabinoid,system,mediates,cardiac,hypertrophy,induced,by,Rosiglitazone,RSG,synthetic,peroxisome,proliferator,activated,receptor,PPARy,which,plays,central,role,regulation,metabolism,analyses,have,suggested,that,associated,increased,cardiovascular,risk,However,mechanisms,underlying,such,adverse,effects,are,still,poorly,understood,Here,found,stimulated,ECS,membrane,lipid,signaling,In,neonatal,cardiomyocytes,level,AEA,upregulated,expression,acyl,phosphatidylethanolamine,phospholipase,key,enzyme,synthesis,downregulated,fatty,acid,hydrolase,FAAH,responsible,degradation,Importantly,type,CB1,through,identified,binding,site,promoter,region,Moreover,both,vitro,vivo,results,showed,inhibition,antagonist,attenuated,indicated,decreased,markers,ANP,BNP,deactivation,mTOR,pathway,size,Thus,these,demonstrated,functions,novel,target,axis,remodeling
AB值：
0.516175
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机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
