Abstract 19013: Effect of Vildagliptin on the Improvement of Survival in Murine Pressure-Overload Heart Failure Model
Glucagon-like peptide-1 (GLP-1) is an incretin hormone, and its analogs have been reported effective in ischemic or non-ischemic heart diseases as well as diabetes mellitus. Dipeptidyl-peptidase IV (DPP-IV) inhibitors that reduce GLP-1 degradation are considered cardioprotective for such pathophysiological states. Since heart failure (HF) is linked to impaired glucose tolerance, we aimed to clarify the effects of DPP-IV inhibitors on HF using pressure-overload hypertrophy model mice (male C57BL6 at 8 weeks of age). Cardiac hypertrophy and HF were induced by transverse aortic constriction (TAC) in a group of mice that were randomised to 2 subgroups, one of which received oral drinking water containing vildagliptin (0.2mg/ml) (TV), and the other received water only (TC). We also made 2 sham operation subgroups, one of which had the same vildagliptin dissolution (SV) and the other was a control (SC). TV had better survival curve than TC (67% vs. 38%, respectively) 14 days after TAC operation. The ratio of heart weight to body weight (mg/g) (6.12 ± 0.69 (SEM) in all TAC vs. 4.99 ± 0.17 in SC, p < 0.05) and the ratio of lung weight to body weight (mg/g) (15.37 ± 1.94, 7.82 ± 1.07, p < 0.05) suggested that death in TAC mice was due to HF. Intraperitoneal glucose tolerance test was done, and we found that blood glucose levels 30 and 120 minutes after intraperitoneal glucose injections were higher in TC than in SC mice (476.4 ± 20.9 vs. 400.5 ± 11.2, and 161.5 ± 9. 4 vs. 127.3 ± 8.3, p < 0.05). Also blood glucose levels 30, 60 and 120 minutes after the injection were significantly lower in TV than in TC (345.1 ± 7.9 vs. 476.4 ± 20.9, 245.5 ± 13.1 vs. 349.6 ± 25.3, and 127.9 ± 8.5 vs. 161.5 ± 9.4, p < 0.05). Of note, no mouse treated with vildagliptin had hypoglycemia. In conclusion, vildagliptin improved the survival rate of pressure overloaded failing mice partly by improving glucose tolerance and by the cardioprotective effect of GLP-1 which, compared to other anti-diabetic drugs, produces no hypoglycemia.
- © 2010 by American Heart Association, Inc.