Abstract 16284: Patient Derived Endothelial Progenitor Cells as a Model to Unravel New Mechanisms of Coronary Artery Disease

Introduction: Endothelial colony forming cells (ECFCs) are progenitor cells that can differentiate into mature endothelial cells. Ability to culture these cells from peripheral blood mononuclear cells (PBMCs) make them a suitable tool for investigation into individual susceptibility to coronary artery disease (CAD). We hypothesise that patient-derived ECFCs provide a model to study endothelial cell signalling in patients with CAD. Here we aim to identify biasing factors in spontaneous growth of ECFCs, and confirm whether they retain an “imprint” of patient disease burden. Methods: ECFCs were purified from patient samples in the BioHEART-CT biobank. Mitochondrial ROS assays (MitoSOX) were performed and protein lysate was collected to determine expression of redox signalling proteins by immunoblotting. CT coronary angiograms were analysed using Gensini scores to determine the burden of disease. Results: Spontaneous growth of ECFCs occurred in 178 of the 828 patients (21.50%). Spontaneous growth was lower in those with obesity (BMI ≥ 30: 15.7%, n = 30/191 vs BMI < 30: 23.2%, n = 148/637, p = 0.03) and higher in hypertensive patients (25.4% n = 81/319 vs normotensive 19.1% n = 97/509, p = 0.03), although growth was not affected by presence of CAD (21.0% n = 59/281 vs CAD- 21.8% n = 119/547, p = 0.8). ECFCs expressed endothelial markers such as CD31 and eNOS, validating their differentiation into endothelial cells. However, ECFCs of patients with CAD expressed higher NADPH oxidase-2 protein level (1.9±0.4 fold-change vs CAD-, n = 13, p = 0.02) and were associated with higher mitochondrial superoxide production (Pearson correlation= 0.66, n = 18, p = 0.003). Conclusion: Spontaneous growth is affected by obesity and hypertension however the impact of this is reasonably small. The biochemical characteristics identified in these cells correlate with the patient’s disease state indicating that they are a helpful tool to further investigate individual susceptibility to CAD.