Abstract 21306: Contrasting Influences of Cardiomyocyte and Endothelial NADPH Oxidase Activation on Post-Myocardial Infarction Cardiac Remodeling
Introduction: NADPH oxidases are a major cardiac source of reactive oxygen species (ROS). Global deletion of NADPH oxidase type 2 (Nox2) protects against cardiac remodeling after myocardial infarction (MI) but the relevant cellular source for this effect is unknown. We investigated the relative importance of Nox2 in cardiomyocytes and endothelial cells in this process.
Methods: Mice with either endothelial-targeted or cardiomyocyte-targeted overexpression of Nox2, and their respective wild-type (WT) littermates, were studied. Permanent ligation of the left coronary artery (or sham operation) with subsequent recovery and four week follow-up was performed.
Results: Mortality post-MI was similar in all groups. Infarct size was similar in endothelial-Nox2 transgenics (Tg) and cardiomyocyte-Nox2 Tg at 2 days post-operatively (41.3 +/− 1.9 % vs. 44.8 +/− 2.6 % of LV area, by MRI late gadolinium enhancement) and at 4 weeks post-operatively (42.3 +/− 2.4 % vs. 42.1 +/− 2.5 %, by infarct length on MRI). Cardiomyocyte hypertrophy in the non-infarct myocardium was present in all groups post-MI but was significantly greater in cardiomyocyte-specific Nox2 Tg (mean area 496 +/− 27 μm2 vs. 382 +/− 16 μm2 in corresponding WT MI; p=0.003 on 2-way ANOVA). Cardiomyocyte-Nox2 Tg also showed significantly greater interstitial fibrosis post-MI (1.54 +/− 0.09 % of LV area vs. 1.17 +/− 0.04 % in corresponding WT MI; p=0.003 on 2-way ANOVA). In contrast, endothelial-Nox2 Tg mice were similar to their respective WT littermates in terms of post-MI cardiac hypertrophy (339 +/− 17 μm2 vs. 325 +/− 22 μm2) and interstitial fibrosis (1.17 +/− 0.16 % vs. 1.28 +/− 0.16 %). Cardiac function (from echocardiography and MRI) was reduced to a similar extent in all post-MI groups throughout the period of study.
Conclusions: Overexpression of Nox2 in cardiomyocytes (but not in endothelial cells) led to a significant increase in post-MI cardiomyocyte hypertrophy and interstitial fibrosis. These results suggest that cardiomyocytes may be the main cellular source of Nox2 contributing to post-MI cardiac remodeling.
- Ventricular remodeling
- Myocardial infarction
- Oxidative stress
- Muscle, cardiac - see Myocardium
- © 2010 by American Heart Association, Inc.