Abstract 17209: Diabetes Mellitus Potentially Can Cause Diastolic Dysfunction
Introduction: Diastolic dysfunction (DD) is observed in about 40% of patients with diabetes mellitus (DM). DM is associated with DD in epidemiological trails. Previously, cardiac oxidation and fibrosis have been associated with DD in animal models. We sought to determine whether these mechanisms occurred in the DM type 2 KK.CgAy mouse model. Furthermore, we sought to determine if advanced glycosylation end products (AGE), oxidative stress, and fibrosis may be involved in causing DD.
Methods: Echocardiography and single cell measures of cardiomyocytes were used to determine if wild type (C57/BL6J) and KK.CgAy mice had DD. Western blotting against dinitorphenylhydrozone derivatizatives detected oxidized protein levels (Oxyblot) and immunohistochemistry was performed to determine collagen levels. Sarcomere function of contraction and relaxation were assessed by IonOptix System under stimulation at 1.0Hz, 4ms duration at 37’C perfusion.
Results: The DM type 2 KK.CgAy mouse model shows DD by echocardiography. The ratio of E ‘/A’ is significantly lower in KK.CgAy compared to C57 control mice (0.73 ± 0.17 vs. control 1.08 ± 0.28, P<0.05). There was no difference in AGE, TGF-β, or collagen levels when comparing control group to KK.CgAy mice. Oxidatively modified proteins under 50 KDa were significantly increased in KK.CgAy mice (3.44 ± 0.09 fold, P<0.01). Indicative of DD, resting sarcomere length was shorter in KK.CgAy mice (1.65 ± 0.01 μ m vs. control 1.83 ± 0.01 μ m, P<0.001). The isolated myocyte relaxation constant, tau, was significantly increased in KK.CgAy mice (0.13 ± 0.01 μ m vs. control 0.08 ± 0.01, P<0.01) indicating relaxation impairment of diasolic dysfunction in DM model.
Conclusion: Our study indicates that DM can cause DD and that the molecular mechanism is associated with oxidative modification of proteins. Fibrosis and advanced glycosylation end products were not associated with DD in the DM type 2 KK.CgAy mouse model.
- © 2011 by American Heart Association, Inc.