Abstract 19979: Endothelium-specific Increase in ROS has Protective Effects on Vascular Endothelium in Ischemic Myocardium
Introduction: Increased ROS is often associated with vascular pathology. Recent findings demonstrated that increases in NADPH oxidase-derived endothelium (EC)-specific ROS improved coronary endothelial function by activating AMPK-eNOS signaling pathway. Here, we examined the effects of EC-ROS on vessel density in post-infarct ischemic myocardium.
Hypothesis: We tested the hypothesis that increased EC-ROS induces AMPK-FOXO1-mediated overexpression of mitochondrial antioxidant MnSOD, which in turn has protective effects on vascular endothelium in ischemic myocardium.
Methods: Our binary (Tet-ON/OFF) conditional transgenic mouse (Tet-Nox2:VE-Cad-tTA) induces 1.8±0.42-fold increase in NADPH oxidase-derived ROS in endothelium. Using these animals, we have induced myocardial infarction by LAD (left anterior descending) ligation.
Results: Co-immunostaining of the ischemic myocardium using anti-CD31 and anti-SMA antibodies demonstrated that there was an increase in capillary density (by 38± 6.45; p<0.05) in Tet-Nox2:VE-Cad-tTA mice with high EC-ROS. Isolated mouse heart ECs showed an increase in AMPK-Foxo1-mediated expression of MnSOD in Tet-Nox2:VE-Cad-tTA mice compared to control. Together, these findings suggest that increase in EC-ROS increases mitochondrial antioxidant MnSOD, which in turn protects coronary endothelium in myocardial ischemia.
Conclusion: This study demonstrates that the endothelial ROS may play an important role in myocardial preservation.
Author Disclosures: E. Shafique: None. K. Reichert: None. B. Colantuono: None. A. Torina: None. E. Harrington: None. F. Sellke: Consultant/Advisory Board; Modest; medicines company, advisory committee, boehringer ingleheim, DSMB. R. Abid: None.
- © 2015 by American Heart Association, Inc.