title: Dipeptidyl-peptidase IV inhibition improves pathophysiology of heart failure and increases survival rate in pressure-overloaded mice.
abstract: Incretin hormones, including glucagon-like peptide-1 (GLP-1), a target for diabetes mellitus (DM) treatment, are associated with cardioprotection. As dipeptidyl-peptidase IV (DPP-IV) inhibition increases plasma GLP-1 levels in vivo, we investigated the cardioprotective effects of the DPP-IV inhibitor vildagliptin in a murine heart failure (HF) model. We induced transverse aortic constriction (TAC) in C57BL/6J mice, simulating pressure-overloaded cardiac hypertrophy and HF. TAC or sham-operated mice were treated with or without vildagliptin. An intraperitoneal glucose tolerance test revealed that blood glucose levels were higher in the TAC than in sham-operated mice, and these levels improved with vildagliptin administration in both groups. Vildagliptin increased plasma GLP-1 levels in the TAC mice and ameliorated TAC-induced left ventricular enlargement and dysfunction. Vildagliptin palliated both myocardial apoptosis and fibrosis in TAC mice, demonstrated by histological, gene and protein expression analyses, and improved survival rate on day 28 (TAC with vildagliptin, 67.5%; TAC without vildagliptin, 41.5%; P < 0.05). Vildagliptin improved cardiac dysfunction and overall survival in the TAC mice, both by improving impaired glucose tolerance and by increasing GLP-1 levels. DPP-IV inhibitors represent a candidate treatment for HF patients with or without DM.
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Takahashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Shin
authors.initials: S
authors.lastname: Ito
authors.forename: Kyung-Duk
authors.initials: KD
authors.lastname: Min
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shindo
authors.forename: Yi
authors.initials: Y
authors.lastname: Yan
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Shoji
authors.initials: S
authors.lastname: Sanada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Asano
authors.forename: Hatsue
authors.initials: H
authors.lastname: Ishibashi-Ueda
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005951:Glucose Tolerance Test; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D013534:Survival; D000077597:Vildagliptin
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D052216:Glucagon-Like Peptide 1; D000077597:Vildagliptin; D000218:Adamantane
keywords: dipeptidyl-peptidase IV inhibitor; heart failure; impaired glucose tolerance