Glucagon-like peptide-1 attenuates cardiac hypertrophy via the AngII/AT1R/ACE2 and AMPK/mTOR/p70S6K pathways  

作　　者：Jing Wang Shaohua Fan Qianfeng Xiong Yu Niu Xin Zhang Junnan Qin Yawei Shi Lihui Zhang 

机构地区：[1]Department of Cardiology,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Shanxi Medical University,Tongji Shanxi Hospital,Tongji Medical College,Huazhong University of Science and Technology,Taiyuan 030032,China [2]Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education,Institute of Biotechnology,Shanxi University,Taiyuan 030006,China [3]Department of Cardiology,Fengcheng People’s Hospital,Fengcheng 331100,China [4]Department of General Medical,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Shanxi Medical University,Tongji Shanxi Hospital,Tongji Medical College,Huazhong University of Science and Technology,Taiyuan 030032,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第9期1189-1197,共9页生物化学与生物物理学报（英文版）

基　　金：the grants from the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province(No.2017-1389);Research Project Supported by Shanxi Scholarship Council of China(No.2020-179);the Applied Basic Research Program in Shanxi Province(No.201801D121202).

摘　　要：Glucagon-like peptide-1(GLP-1),a novel type of glucose-lowering agent,has been reported to exert cardioprotective effects.However,the cardioprotective mechanism of GLP-1 on spontaneous hypertension-induced cardiac hypertrophy has not been fully elucidated.In this study,we revealed that liraglutide or alogliptin treatment ameliorated spontaneous hypertension-induced cardiac hypertrophy,as evidenced by decreased levels of cardiac hypertrophic markers(atrial natriuretic peptide,brain natriuretic peptide,andβ-myosin heavy chain),as well as systolic blood pressure,diastolic blood pressure,mean arterial pressure,and histological changes.Both drugs significantly reduced the levels of angiotensin II(AngII)and AngII type 1 receptor(AT1R)and upregulated the levels of AngII type 2 receptor(AT2R)and angiotensin-converting enzyme 2(ACE2),as indicated by a reduced AT1R/AT2R ratio.Simultaneously,treatment with liraglutide or alogliptin significantly increased GLP-1 receptor expression and adenosine monophosphate-activated protein kinase(AMPK)phosphorylation and downregulated the phosphorylation of mammalian target of rapamycin(mTOR),p70 ribosomal S6 protein kinase,and eukaryotic translation initiation factor 4E binding protein 1 in spontaneous hypertension rats.Furthermore,our data demonstrated that the AMPK inhibitor compound C or mTOR activator MHY1485 inhibited the anti-hypertrophic effect of GLP-1.In summary,our study suggests that liraglutide or alogliptin protects the heart against cardiac hypertrophy by regulating the expression of AngII/AT1R/ACE2 and activating the AMPK/mTOR pathway,and GLP-1 agonist can be used in the treatment of patients with cardiac hypertrophy.

关 键 词：glucagon-like peptide 1 cardiac hypertrophy AMPK/mTOR AT1R/AT2R 

分 类 号：R542.2[医药卫生—心血管疾病]