title: Intermedin attenuates myocardial infarction through activation of autophagy in a rat model of ischemic heart failure via both cAMP and MAPK/ERK1/2 pathways.
abstract: Intermedin is a proopiomelanocortin-derived peptide before opioid promoting cortical hormone, its main function embodies in mononuclear macrophages and neutrophilic granulocytes to inhibit the proinflammatory cytokines. The aim of this study is to determine intermedin attenuates myocardial infarction and its related mechanisms in a rat model of ischemic heart failure. After rat model of ischemic heart failure was set up, myocardial infarction, blood levels of activities of creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) were effectively reduced by treatment with intermedin. Tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in a rat model of ischemic heart failure were recovered by pretreatment with intermedin. Administrate of intermedin availably promoted cAMP contents and suppressed caspase-3 protein in ischemic heart failure rat. ERK1/2 and LC3 protein expression were significantly activated and autophagy was significantly promoted by intermedin in a rat model of ischemic heart failure. These results indicate that intermedin protected rat heart, attenuates myocardial infarction from ischemic heart failure in the rat model. The underlying mechanisms may include upregulation of cAMP, ERK1/2 and LC3 protein expression and activating of autophagy.
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Soochow University Suzhou 215006, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Soochow University Suzhou 215006, China.
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Xuzhou Central Hospital Xuzhou 221009, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Cardiology, Xuzhou Central Hospital Xuzhou 221009, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Soochow University Suzhou 215006, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ling
authors.affiliation: Department of Geriatrics Changhai Hospital of Second Military Medical University Shanghai 200433 China.
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Cardiology, Xuzhou Central Hospital Xuzhou 221009, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zong
authors.affiliation: Department of Cardiology, Xuzhou Central Hospital Xuzhou 221009, China.
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Jiang
mesh_terms: D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006333:Heart Failure / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology; D009479:Neuropeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C499411:Adm2 protein, rat; D009479:Neuropeptides; D053607:Adrenomedullin; D000242:Cyclic AMP; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: ERK1/2; Intermedin; autophagy; cAMP; ischemic heart failure