title: Metformin improves cardiac function in mice with heart failure after myocardial infarction by regulating mitochondrial energy metabolism.
abstract: To investigate whether metformin can improve the cardiac function through improving the mitochondrial function in model of heart failure after myocardial infarction. Male C57/BL6 mice aged about 8 weeks were selected and the anterior descending branch was ligatured to establish the heart failure model after myocardial infarction. The cardiac function was evaluated via ultrasound after 3 days to determine the modeling was successful, and the mice were randomly divided into two groups. Saline group (Saline) received the intragastric administration of normal saline for 4 weeks, and metformin group (Met) received the intragastric administration of metformin for 4 weeks. At the same time, Shame group (Sham) was set up. Changes in cardiac function in mice were detected at 4 weeks after operation. Hearts were taken from mice after 4 weeks, and cell apoptosis in myocardial tissue was detected using TUNEL method; fresh mitochondria were taken and changes in oxygen consumption rate (OCR) and respiratory control rate (RCR) of mitochondria in each group were detected using bio-energy metabolism tester, and change in mitochondrial membrane potential (MMP) of myocardial tissue was detected via JC-1 staining; the expressions and changes in Bcl-2, Bax, Sirt3, PGC-1α and acetylated PGC-1α in myocardial tissue were detected by Western blot. RT-PCR was used to detect mRNA levels in Sirt3 in myocardial tissues. Metformin improved the systolic function of heart failure model rats after myocardial infarction and reduced the apoptosis of myocardial cells after myocardial infarction. Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1α in myocardial tissue of heart failure after myocardial infarction. Metformin decreases the acetylation level of PGC-1α through up-regulating Sirt3, mitigates the damage to mitochondrial membrane potential of model of heart failure after myocardial infarction and improves the respiratory function of mitochondria, thus improving the cardiac function of mice.
authors.affiliation: Department of Geriatrics, General Hospital of Daqing Oil Field, Daqing City, China. Electronic address: sundan0459@sina.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Geriatrics, General Hospital of Daqing Oil Field, Daqing City, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002316:Cardiotonic Agents / Q000494:pharmacology*; D019069:Cell Respiration / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006334:Heart Function Tests; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; C525046:Sirt3 protein, mouse; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D008687:Metformin; D056566:Sirtuin 3
keywords: Heart failure; Metformin; Mitochondrial energy metabolism; PGC-1α; Sirt3