title: Dipeptidyl peptidase-4 inhibitor improves cardiac function by attenuating adverse cardiac remodelling in rats with chronic myocardial infarction.
abstract: What is the central question of this study? Although cardioprotective effects of dipeptidyl peptidase-4 (DPP-4) inhibitors have been demonstrated, their cardiac effects in chronic myocardial infarction (MI) are unclear. We determined the effects of a DPP-4 inhibitor on cardiac function and remodelling in rats with chronic MI. What is the main finding and its importance? We demonstrated, for the first time, that DPP-4 inhibitor, but not metformin, exerted similar efficacy in improving cardiac function and attenuating cardiac fibrosis compared with enalapril in rats with chronic MI. These findings reveal benefits additional to the glycaemic control by the DPP-4 inhibitor in chronic MI, and it might become the new drug of choice for MI in patients with diabetes mellitus. Adverse cardiac remodelling after myocardial infarction (MI) leads to progressive heart failure. Dipeptidyl peptidase-4 (DPP-4) inhibitors are new antidiabetic drugs that exert cardioprotection. However, their role in cardiac function and remodelling in chronic MI is unclear. We hypothesized that the DPP-4 inhibitor vildagliptin reduces adverse cardiac remodelling and improves cardiac function in rats with chronic MI. These effects were also compared with enalapril and metformin. Male Wistar rats (n = 36) with chronic MI induced by ligation of the left anterior descending coronary artery were divided into six groups to receive vehicle, vildagliptin (3 mg kg(-1)  day(-1) ), metformin (30 mg kg(-1)  day(-1) ), enalapril (10 mg kg(-1)  day(-1) ), combined metformin and enalapril or combined vildagliptin and enalapril for 8 weeks. At the end of the study, plasma malondialdehyde (MDA), heart rate variability (HRV), left ventricular (LV) function, pathological and biochemical studies of cardiac remodelling were investigated. Our study demonstrated that rats with chronic MI had increased oxidative stress levels, depressed HRV, adverse cardiac remodelling, indicated by cardiac fibrosis, and LV dysfunction. Treatment with vildagliptin or enalapril significantly decreased oxidative stress, attenuated cardiac fibrosis and improved HRV and LV function. We conclude that vildagliptin exerts similar cardioprotective effects to enalapril in attenuating oxidative stress and cardiac fibrosis and improving cardiac function in rats with chronic MI. Metformin does not provide these benefits in this model. Moreover, addition of either metformin or vildagliptin to enalapril does not provide additional benefit in attenuating cardiac remodelling or improving LV function compared with enalapril alone.
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Tharnwimol
authors.initials: T
authors.lastname: Inthachai
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Suree
authors.initials: S
authors.lastname: Lekawanvijit
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Sirinart
authors.initials: S
authors.lastname: Kumfu
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nattayaporn
authors.initials: N
authors.lastname: Apaijai
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Wanpitak
authors.initials: W
authors.lastname: Pongkan
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Department of Oral Biology and Diagnostic Science, Faculty 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 Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology; D005355:Fibrosis; D006339:Heart Rate / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008687:Metformin / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D017208:Rats, Wistar; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*; D000077597:Vildagliptin
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; 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