title: Intermedin1-53 protects against cardiac hypertrophy by inhibiting endoplasmic reticulum stress via activating AMP-activated protein kinase.
abstract: OBJECTIVE
  Intermedin (IMD), a novel member of the calcitonin/calcitonin gene-related peptide family, is involved in maintaining circulatory homeostasis and is a protective factor of heart and vessel. Here, we investigated the effects of IMD on cardiac hypertrophy in vivo and in vitro and explored the mechanisms involved.
  
  
  RESULTS
  IMD1-53 (100 ng/kg/h) was systemically administered to rats with cardiac hypertrophy induced by abdominal aortic constriction (AAC) by a mini-osmotic pump the next day after surgery continuously for 4 weeks. The AAC-treated rats before IMD infusion showed increased IMD content and expression of its receptors in the hearts. In-vivo administration of IMD1-53 greatly attenuated the cardiac hypertrophy as shown by heart weight to body weight ratio (HW/BW), haemodynamics, echocardiography, histological analyses and expression of hypertrophic markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) induced by AAC. IMD1-53 treatment significantly reduced the myocardial protein expression of endoplasmic reticulum stress (ERS) markers such as glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-12, whereas the protein level of phosphorylated AMP-activated protein kinase (p-AMPK) was upregulated with IMD1-53 treatment, which was further confirmed in cultured cardiomyocytes. Concurrently, cardiomyocyte apoptosis in vivo and in vitro was ameliorated by IMD1-53 treatment. The inhibitory effects of IMD1-53 on ERS and apoptosis were eliminated on pretreatment with compound C, an AMPK inhibitor.
  
  
  CONCLUSIONS
  IMD1-53 could exert its cardioprotective effect on cardiac hypertrophy by inhibiting myocardial ERS and apoptosis, possibly via activation of AMPK signalling.
authors.affiliation: aLaboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University bKey Laboratory of Molecular Cardiovascular Science, Ministry of Education cDepartment of Pathogen Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Lu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: Zhang
authors.forename: Yue-Long
authors.initials: YL
authors.lastname: Hou
authors.forename: Yan-Rong
authors.initials: YR
authors.lastname: Yu
authors.forename: Mo-Zhi
authors.initials: MZ
authors.lastname: Jia
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Qi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D053607:Adrenomedullin / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D053454:Caspase 12 / Q000378:metabolism; D002478:Cells, Cultured; D004452:Echocardiography; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D055372:AMP-Activated Protein Kinases; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D022762:CCAAT-Enhancer-Binding Proteins; D053454:Caspase 12; D006360:Heat-Shock Proteins; D020097:Natriuretic Peptide, Brain; D009479:Neuropeptides; C499411:Adm2 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP