Abstract 868: Cardiac-Specific Overexpression of Catalase Prevents Progressive Left Ventricular Remodeling and Failure in Gq-Overexpressing Transgenic Mice
Background: In cardiac myocytes in vitro hydrogen peroxide (H2O2) causes hypertrophy and apoptosis, events associated with myocardial remodeling and failure. Transgenic mice with cardiac-specific overexpression of Gq develop a dilated cardiomyopathy. The role of H2O2 in mediating myocardial remodeling and failure in vivo is not clear.
Methods: To test the hypothesis that H2O2 mediates pathologic remodeling, Gq and wild type (WT) mice were cross-bred with transgenic mice having cardiac-specific overexpression of catalase, and the males were followed 20 weeks by echocardiography (n = 5 - 9 per group).
Results: In Gq (vs. WT) mice, left ventricular (LV) end-diastolic dimension (EDD) was increased and LV fractional shortening (FS) was decreased at 4 weeks, the earliest age studied, and progressively deteriorated through 20 weeks (Figure⇓). Myocardial catalase overexpression in Gq mice had no effect on EDD or FS at 4 weeks, but prevented subsequent changes in EDD and FS over weeks 12 through 20 (Figure⇓; * p<0.001 vs. Gq). At 20 weeks, maximal exercise capacity (motorized treadmill) was 337±36 meters in WT mice and decreased by 38% to 210±9 meters in Gq mice (p<0.05 vs. WT), but was preserved in Gq/catalase mice (332±39 meters; p=NS vs. WT). Increased heart, LV and lung weights in Gq mice were attenuated in Gq/catalase mice.
Conclusion: While catalase had no effect on development of dilated cardiomyopathy, it prevented the subsequent progression to LV failure. The initiating cardiomyopathy in Gq mice appears to be independent of reactive oxygen species, whereas the progressive remodeling and failure that ensues is highly dependent on catalase-sensitive reactive oxygen species.