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Year:: 2021
Contributor:: Bellam, Krishna (Author); Teixeira, Rayane (Author); Wipf, Peter (Author); Sellke, Frank (Author); Abid, Ruhul (Author); Brown University. Alpert Medical School. Scholarly Concentration Program. Non-Scholarly Concentrator (research program)
Subject:: Blood-vessels--Growth; Endothelial cells

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Abstract:: Background/ State the problem: Cardiovascular disease (CVD) is the leading cause of death and morbidity in the USA. The most common type of CVD, Coronary Artery Disease (CAD), kills roughly 360,000 people per year. Rationale: Augmentation of angiogenesis is a promising new therapeutic strategy for the treatment of patients with CAD to expand the myocardial microvascular network, which improves myocardial function by increasing blood flow to ischemic areas of the heart. Recent studies have demonstrated both harmful and beneficial effects of reactive oxygen species (ROS) on the cardiovascular system and angiogenesis; these outcomes are determined by the interactions between ROS in various subcellular compartments. The role of ROS, specifically mitochondrial ROS, in modulating atrial endothelial cell (EC) metabolism, proliferation, and angiogenesis has been of particular interest to our lab. We hypothesize that decreasing the level of mitochondrial-ROS will improve dNTP synthesis and, thus, angiogenesis in atrial endothelial cells ex vivo. Method/ Approach/Results/Conclusion Eight EC-specific transgenic NOX-expressing animals will be split into two binary conditional groups: Tet-ON; Control (n=4) and Tet-OFF;Nox-OE (n=4). Mice at 20 weeks of age will be treated with or without tetracycline for four weeks prior to atrial harvesting and sectioning (24 weeks). Patients (non-DM, controlled-DM, uncontrolled-DM) undergoing coronary artery bypass surgery will simultaneously be enrolled (n=5/group) and their atrial tissues will be collected. For ex vivo angiogenic assays using atrial tissue from NOX-OE mice and humans, fibrin clot method will be employed with or without mito-antioxidants XJB-5-131 (0.5 μM) or JP4-039 (0.5 μM). Sprouting density, total vessel network length, and branching points will all be subsequently analyzed using Angiotool software. This data will be compared using one-factor or two-factor ANOVA and whenever significance (p<0.05) is indicated, a Neumann-Keuls test for multiple comparisons will be used to compare between groups. We anticipate improved atrial EC proliferation and angiogenesis in both human and mouse atrial tissue using mito-antioxidants XJB-5-131 and JP4-039.
Notes:: Scholarly concentration: Non-Scholarly Concentrator

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Bellam, Krishna, Teixeira, Rayane, Wipf, Peter, et al., "Reduction of mito-ROS via mitochondrial antioxidants in atrial endothelial cells induces angiogenesis." (2021). Warren Alpert Medical School Academic Symposium. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:7eaw6agw/

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Warren Alpert Medical School Academic Symposium

The Warren Alpert Medical School Academic Symposium is an annual event at Warren Alpert Medical School of Brown University that provides Year II medical students a venue to present their summer research in a poster format. Participation in the Symposium …
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Reduction of mito-ROS via mitochondrial antioxidants in atrial endothelial cells induces angiogenesis.