title: Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats.
abstract: BACKGROUND
  Heart failure with left ventricular (LV) hypertrophy is often associated with insulin resistance and inflammation. Recent studies have shown that dipeptidyl peptidase 4 (DPP4) inhibitors improve glucose metabolism and inflammatory status. We therefore evaluated whether vildagliptin, a DPP4 inhibitor, prevents LV hypertrophy and improves diastolic function in isoproterenol-treated rats.
  
  
  METHODS
  Male Wistar rats received vehicle (n = 20), subcutaneous isoproterenol (2.4 mg/kg/day, n = 20) (ISO), subcutaneous isoproterenol (2.4 mg/kg/day + oral vildagliptin (30 mg/kg/day, n = 20) (ISO-VL), or vehicle + oral vildagliptin (30 mg/kg/day, n = 20) (vehicle-VL) for 7 days.
  
  
  RESULTS
  Blood pressure was similar among the four groups, whereas LV hypertrophy was significantly decreased in the ISO-VL group compared with the ISO group (heart weight/body weight, vehicle: 3.2 ± 0.40, ISO: 4.43 ± 0.39, ISO-VL: 4.14 ± 0.29, vehicle-VL: 3.16 ± 0.16, p < 0.05). Cardiac catheterization revealed that vildagliptin lowered the elevated LV end-diastolic pressure observed in the ISO group, but other parameters regarding LV diastolic function such as the decreased minimum dp/dt were not ameliorated in the ISO-VL group. Histological analysis showed that vildagliptin attenuated the increased cardiomyocyte hypertrophy and perivascular fibrosis, but it did not affect angiogenesis in cardiac tissue. In the ISO-VL group, quantitative PCR showed attenuation of increased mRNA expression of tumor necrosis factor-α, interleukin-6, insulin-like growth factor-l, and restoration of decreased mRNA expression of glucose transporter type 4.
  
  
  CONCLUSIONS
  Vildagliptin may prevent LV hypertrophy caused by continuous exposure to isoproterenol in rats.
authors: Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. miyoshit@cc.okayama-u.ac.jp.
authors: Toru
authors: T
authors: Miyoshi
authors: Kazufumi
authors: K
authors: Nakamura
authors: Masashi
authors: M
authors: Yoshida
authors: Daiji
authors: D
authors: Miura
authors: Hiroki
authors: H
authors: Oe
authors: Satoshi
authors: S
authors: Akagi
authors: Hiroki
authors: H
authors: Sugiyama
authors: Kaoru
authors: K
authors: Akazawa
authors: Tomoko
authors: T
authors: Yonezawa
authors: Jun
authors: J
authors: Wada
authors: Hiroshi
authors: H
authors: Ito
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D008297:Male; D009570:Nitriles / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D000077597:Vildagliptin
chemical_list: D000318:Adrenergic beta-Agonists; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin; D000218:Adamantane