Abstract 11313: Cardiac-Specific Overexpression of Catalase Attenuates Myocardial Hypertrophy and Diastolic Dysfunction in Diet-Induced Metabolic Syndrome in Mice
Background: We showed that an “American” diet high in fat and sugar (HFHS) induces metabolic heart disease (MHD) characterized by left ventricular (LV) hypertrophy, fibrosis and diastolic dysfunction that are associated with increased myocardial oxidative stress. We now test the hypothesis that H2O2 mediates metabolic heart disease by examining the ability of cardiac-specific overexpression of catalase to prevent HFHS-induced MHD.
Methods: Beginning at 10 weeks of age, FVB mice with cardiac-specific overexpression of catalase or wild type (WT) (n=6-8 per group) were fed a HFHS or control diet for 8 months. LV dimensions and function were measured monthly by echocardiography. Myocardial fibrosis was measured by picrosirius red staining.
Results: In WT mice, HFHS feeding led to progressive LV wall thickening and diastolic dysfunction characterized by prolongation of the isovolumetric relaxation and deceleration times, decreases in the ratio of peak early and late mitral inflow velocity and myocardial peak early diastolic velocity (Em, Figure) indicative of slowed relaxation. Catalase overexpression partially attenuated the increase in LV wall thickness, and completely prevented the development of diastolic dysfunction as reflected by normalization of the isovolumetric relaxation and deceleration times, the ratio of peak early and late mitral inflow velocity and Em (Figure). Myocardial fibrosis was increased in WT mice fed a HFHS diet at 8 month (3.2±0.6% vs. 1.6±0.3% in WT mice fed a control diet, P<0.05), and the increase was prevented by catalase overexpression (2.0±0.5%, P<0.05 vs. WT mice fed a HFHS diet).
Conclusion: H2O2, derived from and/or acting within the cardiac myocyte, plays an important role in mediating diet-induced MHD by contributing to LV hypertrophy, fibrosis and diastolic dysfunction.
- © 2013 by American Heart Association, Inc.