title: Metformin protects the myocardium against isoproterenol-induced injury in rats through alleviating endoplasmic reticulum stress.
abstract: Clinical studies have suggested that metformin, a widely used antidiabetic agent, exerts a direct cardioprotective effect on cardiovascular disease in addition to its blood glucose-lowering activity. This study was designed to identify the role of metformin in rats with isoproterenol (ISO)-induced myocardial injury and to investigate its underlying mechanism. A rat model of myocardial ischemic injury was established by the subcutaneous injection of a high dose of ISO, a beta-adrenergic agonist. The results showed that pretreatment of metformin significantly reduced rat mortality induced by ISO, attenuated the increased plasma lactate dehydrogenase activity and myocardium malondialdehyde level, alleviated the hemodynamic disturbance, inhibited the upregulated gene expression of myocardial probrain natriuretic peptide and alleviated the myocardial morphological injury and apoptosis induced by ISO. Furthermore, western blot analysis showed that metformin suppressed the overexpression of the endoplasmic reticulum stress (ERS) markers cleaved caspase-12 and CEBP-homologous protein induced by ISO and increased the phosphorylation of AMP-activated protein kinase (AMPK). In conclusion, these data suggest that metformin might protect the myocardium against acute ischemic injury in rats at least partially by activating AMPK and alleviating aberrant ERS. These findings might provide further experimental evidence for treating patients at risk of ischemic heart disease with metformin.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Huaiqiu
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Geriatrics and Gerontology, Beijing Huaxin Hospital, the First Affiliated Hospital of Tsinghua University, Beijing, China.
authors.forename: Gaigai
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China.
authors.forename: Jinrui
authors.initials: J
authors.lastname: Chang
authors.affiliation: Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China.
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China.
authors.forename: Yongfen
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002316:Cardiotonic Agents; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D006439:Hemodynamics / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007545:Isoproterenol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D008315:Malondialdehyde; D008687:Metformin; D007770:L-Lactate Dehydrogenase; D055372:AMP-Activated Protein Kinases; D007545:Isoproterenol