Abstract 20677: Critical Protective Role of Myocardial Extracellular Superoxide Dismutase (SOD3) in Pressure Overload-Induced Cardiac Oxidative Stress and Hypertrophy

We recently reported that a transgenic (TG) mouse model with cardiac-specific overexpression of a dominant-negative (DN) mutant (V204A) of NADPH oxidase (NOX) subunit p67phox attenuated transverse aortic constriction (TAC)-induced increase of reactive oxygen species (ROS) and cardiac hypertrophy vs that in the wild type (WT). In this study, we attempted to explore the mechanisms of these findings & hypothesized that myocardial SOD3 play a critical protective role. Using 4-hydroxynonenal staining, we found TAC-induced membrane lipid peroxidation is reduced in DN-p67 TG mouse left ventricle (54%↓ vs WT, p<0.05). The expression profile of antioxidants was determined, the mRNA expression of SOD3 (3-fold↑) and thioredoxin1 (Trx1, 3.8-fold↑) is significantly increased (p<0.05) in WT-TAC mice vs WT-sham by qRT-PCR; whereas there is no difference among the WT-sham, TG-sham & TG-TAC. In contrast, the expression of other antioxidants including SOD1, SOD2, catalase, Trx2, Nrf2, NQO1, and glutaredoxin was not changed...