Introduction: Recent findings from our lab demonstrated that modulation of NADPH oxidase-derived ROS for a short period (4 weeks), but not long period (20 weeks), improves coronary endothelial cell proliferation in vitro and aortic sprouting angiogenesis ex vivo.
Hypothesis: We hypothesized that whereas short-term increase in endothelial ROS will improve post-MI cardiac function by increased coronary angiogenesis, long-term exposure to ROS will not.
Methods: Tetracycline (Tet)-ON/Tet-OFF binary transgenic mice, Tet-Nox2:VE-Cad-tTA (Tg-Nox2), were used as a model for endothelium-specific increase in the expression of the catalytic subunit of NADPH oxidase resulting in increased ROS. Tet-ON and Tet-OFF Tg-Nox2 mice that were exposed to 4 weeks (short-term) and 16 weeks (long-term) of increased EC-ROS were subject to LAD ligation.
Results: We demonstrate that there was an increase in capillary density (by 38± 6.45; p<0.05) and angiogenesis (by 2-fold) in short-term Tg-Nox2 post-MI myocardium but not in long-term Tg-Nox2. Short-term, but not long-term, Tg-Nox2 animals showed reduction in infarct size by Trichrome staining and improvement in cardiac function including EF, LVEDV and LVESV by echocardiography.
Conclusion: These findings suggest that a short, but not long, exposure to increased EC-ROS play an important role in cardiovascular health and myocardial preservation in the post-MI heart.