Abstract 20592: Selective Inhibition of Myocardial NADPH Oxidase Attenuates Pressure-Overload-Induced Cardiac Hypertrophy in Aged Transgenic Mice with Cardiac-Specific Overexpression of a Dominant-Negative Mutant of p67phox
We recently reported a transgenic (Tg) mouse model with cardiac-specific overexpression of a dominant-negative (DN) mutant (V204A) of NADPH oxidase (NOX) subunit p67phox that inhibits NOX activity. In order to test the role of NOX/p67phox in pressure-overload-induced cardiac hypertrophy in aged adult mice, age-, gender- and body weight (BW)-matched Tg and wild type (WT) C57BL/6 mice (0.5∼1 year old) were subjected to thoracic aortic constriction (TAC) or sham operation. Eight-week post TAC, 2-D echocardiography (echo) was performed to determine the following cardiac parameters: left ventricular myocardial area (LVMA); LV wall thickness at the end diastole; LV internal dimension at end diastole (IDd), LV end-diastolic volume (EDV), LV ejection fraction (EF), LV mass&TAC pressure gradient. Mice were divided into 8 groups (4 groups/gender, 6 mice/group) including WT-sham, WT-TAC, Tg-sham&Tg-TAC. Data were analyzed by one-way ANOVA with post-hoc Newman-Kuels test. The LVEDV, LVIDd&BW were similar among groups in each gender. The LVEF (range: 46–66%) is not statistically different among all groups. The TAC pressure gradient was >36 mmHg in TAC mice. Tg-sham showed a trend of reduction in LVMA, LV mass&wall thickness vs. WT-sham (Table 1), but was not statistically different. The WT-TAC mice showed significant increase in LVMA, LV mass&wall thickness indicating LV hypertrophy; whereas the Tg-TAC mice only showed minor increase in the above parameters that were not statistically different from Tg-sham. In addition, these parameters in Tg-TAC mice were also significantly (p<0.05) smaller than those in WT-TAC mice, suggesting TAC-induced LV hypertrophy was attenuated in Tg mice. Our echo data were also confirmed by our results of heart weight/BW ratio and histological study of the LV myocardium. In summary, our results showed, for the first time, that selective inhibition of myocardial NOX attenuated pressure-overload-Induced cardiac hypertrophy in aged adult mice.
- © 2010 by American Heart Association, Inc.