title: Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction.
abstract: Adverse cardiac remodeling after myocardial infarction (MI) leads to progressive heart failure. Obese-insulin resistance increases risks of MI and heart failure. Although dipeptidyl peptidase-4 (DPP4) inhibitor is known to exert cardioprotection, its effects on adverse remodeling after MI in obese-insulin-resistant rats are unclear. We hypothesized that DPP4 inhibitor reduces adverse left ventricular (LV) remodeling and LV dysfunction in obese-insulin-resistant rats with MI. Rats were fed either normal diet (ND) or high-fat diet (HFD) for 12 weeks to induce obese-insulin resistance, followed by left anterior descending coronary artery ligation to induce MI. Then, rats in each dietary group were divided into five subgroups to receive vehicle, enalapril (10mg/kg/day), metformin (30mg/kg/day), DPP4 inhibitor vildagliptin (3mg/kg/day), or combined metformin and vildagliptin for 8 weeks. Heart rate variability (HRV), LV function, pathological and biochemical studies for LV remodeling, and cardiomyocyte apoptosis were determined. Obese-insulin-resistant rats had severe insulin resistance and LV dysfunction. HFD rats had a higher mortality rate than ND rats, and all treatments reduced the mortality rate in obese-insulin-resistant rats. Although all drugs improved insulin resistance, HRV, LV function as well as reduced cardiac hypertrophy and fibrosis, vildagliptin effectively reduced cardiomyocyte cross-sectional areas more than enalapril and was related to markedly decreased ERK1/2 phosphorylation. In ND rats with MI, metformin neither improved LV ejection fraction nor reduced cardiac fibrosis. The infarct size and transforming growth factor-β expression were not different among groups. In obese-insulin-resistant rats with chronic MI, DPP4 inhibitor vildagliptin exerts better cardioprotection than enalapril in attenuating adverse LV remodeling.
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand.
authors.forename: Nattayaporn
authors.initials: N
authors.lastname: Apaijai
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Tharnwimol
authors.initials: T
authors.lastname: Inthachai
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Department of PathologyFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Suree
authors.initials: S
authors.lastname: Lekawanvijit
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand Department of Oral Biology and Diagnostic SciencesFaculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand nchattip@gmail.com.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004656:Enalapril / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects; D011759:Pyrrolidines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000187:drug effects; D000077597:Vildagliptin
chemical_list: D002316:Cardiotonic Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D004656:Enalapril; D008687:Metformin; C000602659:DPP4 protein, rat; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane
keywords: metformin; myocardial infarction; obese-insulin-resistant rats; vildagliptin