Abstract 17169: Endothelium-Specific Reduction in Mitochondrial ROS Induces Coronary Angiogenesis in Ischemic Myocardium via Activation of PI3k/Akt/ERG, ERK1/2, and Jag-1 Signaling

• Published in: Circulation (New York, N.Y.) N.Y.), 2020-11, Vol.142 (Suppl_3 Suppl 3), p.A17169-A17169
• Main Authors: Brinck Teixeira, Rayane, Pfeiffer, Melissa, Karbasiafshar, Catherine, Blume Corssac, Giana, Ahsan, Nagib, Sellke, Frank W, Abid, Ruhul
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.142.suppl_3.17169

IntroductionGlobal reduction in reactive oxygen species (ROS) failed to improve outcomes in cardiovascular disease patients. Recent reports suggest that subcellular, rather than global ROS, play a crucial role in endothelial cell (EC) health. To that end, we generated a novel transgenic mouse model that overexpresses mitochondrial antioxidant MnSOD in EC-specific manner (MnSODVE-OE). HypothesisWe hypothesized that decreased EC mitochondrial-ROS will improve post-myocardial infarction (MI) cardiac function by inducing coronary angiogenesis in ischemic myocardium. MethodsMnSODVE mice were assigned to Tet-ON (control) or Tet-OFF (MnSODVE-OE) group. To turn off the transgene, Tetracycline (Tet) (2mg/kg) was added to the drinking water (Tet-ON), while Tet-OFF mice did not receive Tet. Both groups underwent left anterior descending coronary artery (LAD) ligation surgery to mimic acute MI. Echocardiography was done 28 days after LAD ligation. Capillaries, arteriole density, and proliferating ECs were measured in heart sections using anti-CD31, anti-αSMA, and anti-PCNA immunofluorescence. Western blot, proteomic and phosphoproteomic analyses of mouse heart ECs isolated from MnSODVE (Tet-ON and Tet-OFF) animals were performed to study modulation of signaling cascades. ResultsMnSODVE-OE mice demonstrated improved cardiac function (EF and FS increased by 16±7.87% and 21.73±10.31%, respectively, p