Email updates

Keep up to date with the latest news and content from Cardiovascular Diabetology and BioMed Central.

Open Access Highly Accessed Original investigation

Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats

Toru Miyoshi1*, Kazufumi Nakamura2*, Masashi Yoshida3, Daiji Miura4, Hiroki Oe5, Satoshi Akagi2, Hiroki Sugiyama2, Kaoru Akazawa2, Tomoko Yonezawa6, Jun Wada7 and Hiroshi Ito2

Author Affiliations

1 Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

2 Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Okayama 700-8558, Japan

3 Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

4 Division of Basic and Clinical Medicine, agano College of Nursing, Nagano, Japan

5 Center of Ultrasonic Diagnostics, Okayama University Hospital, Okayama, Japan

6 Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

7 Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

For all author emails, please log on.

Cardiovascular Diabetology 2014, 13:43  doi:10.1186/1475-2840-13-43

Published: 13 February 2014

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.

Keywords:
Cardiac hypertrophy; Dipeptidyl peptidase 4 inhibitor; Inflammation; Left ventricular diastolic dysfunction