PMID- 34357376 OWN - NLM STAT- MEDLINE DCOM- 20220120 LR - 20220120 IS - 1745-7270 (Electronic) IS - 1672-9145 (Linking) VI - 53 IP - 9 DP - 2021 Aug 31 TI - Glucagon-like peptide-1 attenuates cardiac hypertrophy via the AngII/AT1R/ACE2 and AMPK/mTOR/p70S6K pathways. PG - 1189-1197 LID - 10.1093/abbs/gmab099 [doi] AB - 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, and beta-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. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Wang, Jing AU - Wang J AD - 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. FAU - Fan, Shaohua AU - Fan S AD - Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, China. FAU - Xiong, Qianfeng AU - Xiong Q AD - Department of Cardiology, Fengcheng People's Hospital, Fengcheng 331100, China. FAU - Niu, Yu AU - Niu Y AD - 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. FAU - Zhang, Xin AU - Zhang X AD - Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, China. FAU - Qin, Junnan AU - Qin J AD - 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. FAU - Shi, Yawei AU - Shi Y AD - Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, China. FAU - Zhang, Lihui AU - Zhang L AD - 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. LA - eng GR - 201801D121202/the Applied Basic Research Program in Shanxi Province/ GR - 2020-179/Research Project Supported by Shanxi Scholarship Council of China/ GR - 2017-1389/the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province/ PT - Journal Article PL - China TA - Acta Biochim Biophys Sin (Shanghai) JT - Acta biochimica et biophysica Sinica JID - 101206716 RN - 0 (4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine) RN - 0 (Cardiotonic Agents) RN - 0 (Morpholines) RN - 0 (Piperidines) RN - 0 (Receptor, Angiotensin, Type 1) RN - 0 (Triazines) RN - 11128-99-7 (Angiotensin II) RN - 56HH86ZVCT (Uracil) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.4.3 (Adenylate Kinase) RN - EC 3.4.17.23 (Ace2 protein, rat) RN - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) RN - JHC049LO86 (alogliptin) SB - IM MH - Adenylate Kinase/antagonists & inhibitors/*metabolism MH - Angiotensin II/*metabolism MH - Angiotensin-Converting Enzyme 2/*metabolism MH - Animals MH - Blood Pressure/drug effects MH - Cardiomegaly/etiology/metabolism/pathology/prevention & control MH - Cardiotonic Agents/pharmacology/therapeutic use MH - Cell Line MH - Disease Models, Animal MH - Glucagon-Like Peptide 1/*pharmacology/therapeutic use MH - Hypertension/complications MH - Liraglutide/pharmacology/therapeutic use MH - Male MH - Morpholines/pharmacology MH - Myocytes, Cardiac/drug effects MH - Piperidines/pharmacology/therapeutic use MH - Rats MH - Receptor, Angiotensin, Type 1/*metabolism MH - Renin-Angiotensin System/drug effects MH - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/*metabolism MH - Triazines/pharmacology MH - Uracil/analogs & derivatives/pharmacology/therapeutic use OTO - NOTNLM OT - AMPK/mTOR OT - AT1R/AT2R OT - cardiac hypertrophy OT - glucagon-like peptide 1 EDAT- 2021/08/07 06:00 MHDA- 2022/01/21 06:00 CRDT- 2021/08/06 12:24 PHST- 2021/01/03 00:00 [received] PHST- 2021/08/07 06:00 [pubmed] PHST- 2022/01/21 06:00 [medline] PHST- 2021/08/06 12:24 [entrez] AID - 6343195 [pii] AID - 10.1093/abbs/gmab099 [doi] PST - ppublish SO - Acta Biochim Biophys Sin (Shanghai). 2021 Aug 31;53(9):1189-1197. doi: 10.1093/abbs/gmab099.