Abstract 15552: Resolution of Pressure Overload Effects by Carnosine Supplementation in a Mouse Model of Cardiac Hypertrophy
Pathological left ventricular hypertrophy (LVH) is a key risk factor in the development of heart failure and cardiomyopathy. Development of LVH is characterized by an increase in the production of reactive oxygen species (ROS) and the byproducts of oxidized lipids such as 4-hydroxy-trans-2-nonenal (HNE). Both ROS and HNE can be quenched by the endogenous dipeptide carnosine present in high levels (70-100μM) in the heart. However, the role of carnosine in preventing cardiac injury is unclear. Here we report that trans-aortic constriction (TAC) for 2 weeks led to the accumulation of HNE-modified proteins in mouse hearts and the levels of carnosine were significantly suppressed after 8 weeks of TAC. Based on these results we hypothesized that the supplementation of octyl-D-carnosine (ODC), a non-hydrolysable carnosine analog, would attenuate left ventricular remodeling by sequestering reactive oxidant species. Mice were subjected to 8 weeks of TAC and fed 50 mg/kg ODC in water. No changes were observed in the echocardiographic indices of mice fed 50 mg/kg ODC compared with untreated mice. After 4 weeks of TAC LV fractional shortening (FS) showed a significant decrease (29±2%) compared with sham-operated mice (44±1%); whereas, ODC-treated TAC mice had preserved LV function (44±2%). Similarly, LV function in ODC-treated mice after 8 weeks TAC was preserved compared with non-treated TAC mice (FS, 41±3% vs 27±5% p<0.01). LV internal dimension at systole (LVIDS) was increased significantly in non-treated TAC mice compared to ODC treated TAC mice (3.1±0.4mmHg vs 2±0.1mmHg, p<0.05). Corroborating the hemodynamic analysis the LV weight indexed to body weight was greater in non-treated TAC mice compared with the ODC treated TAC mice (7.3±0.7 vs. 6.5±0.02mg, p<0.05). These data suggest that replenishing the carnosine pool by dietary supplementation prevents LV remodeling in mice and strengthen the rationale for testing the efficacy of carnosine in preventing cardiac hypertrophy and heart failure in humans.
- © 2011 by American Heart Association, Inc.