Abstract 20505: Endothelium Specific Mitochondrial ROS in Ischemic Myocardium
Introduction: Ischemic heart disease (IHD) is one of the leading causes of death in the United States. Reactive oxygen species (ROS) are increased during cardiovascular diseases including IHD. Recent findings from our and other labs showing modulation of NADPH oxidase-derived cytosolic ROS improves vascular endothelial function and angiogenic potential of coronary endothelial cells (EC) suggest importance of the subcellular localization of ROS in vascular endothelium. In the current study, we wanted to examine the role of modulation of mitochondrial ROS (mito-ROS) on coronary EC in ischemic myocardium.
Hypothesis: We hypothesized that a decrease in mito-ROS will improve EC proliferation by counteracting increased ROS in the cytosol of EC in ischemic myocardium.
Methods: Tetracycline (Tet)-ON/Tet-OFF binary transgenic mice, Tet-SOD2:VE-Cad-tTA, were used as a model for increased expression of mitochondrial antioxidant MnSOD and decreased mito-ROS. Cultured ECs were used for SOD activity assays and ROS (pC-Hyper) assays to examine the levels of MnSOD and mito-ROS in Tet-OFF animals. LAD ligation and aortic sprouting assays were used as a model for in vivo myocardial ischemia and ex vivo EC proliferation assays, respectively.
Results: SOD and ROS assays showed an increase in MnSOD activity and decrease in mito-ROS in Tet-OFF compared to Tet-ON animals. Aortic sprouting assay showed a significant increase in vessel density, branching index and total vessel length in Tet-OFF animals compared to Tet-ON. LAD model demonstrated an increase in capillary vessel density in ischemic myocardium of Tet-OFF animals compared to Tet-ON.
Conclusion: We have established an animal model with EC-specific overexpression of mitochondrial antioxidant MnSOD with corresponding decrease in mito-ROS. Our binary transgenic model demonstrate that decrease in mito-ROS can counteract the adverse effects of increased cytosolic ROS in ischemic myocardium. We will also present data demonstrating effects of decreased mito-ROS in EC on cardiac function in ischemic myocardium.
Author Disclosures: B. Colantuono: None. E.O. Harrington: None. F.W. Sellke: None. M. Abid: None.
- © 2016 by American Heart Association, Inc.