Diabetes induced hyperglycemia increases the risk of cardiovascular complications as it impacts vascular endothelial cells causing vascular dysfunction. Endothelial progenitor cells (EPCs) have been suggested to participate in the repair of vascular endothelial cells once they are impacted by hyperglycemia in diabetic patients. This research aims to test the EPC subtype blood outgrowth endothelial cells (BOECs) and their ability to survive and function under chronic hyperglycemic conditions. For that, we studied BOECs viability, response to shear stress, angiogenesis ability, and barrier function under normoglycemic (5.5mM) and hyperglycemic (25mM) conditions. The results have shown significant effects of chronic hyperglycemic conditions on cell proliferation (n=3, p<0.05), and migration (n=3, p<0.05) which were decreased when compared to control. Cells responses to shear stress were not affected under these conditions. There was a trend towards an increase in permeability as indicated by barrier function assays. The decrease in those endothelial cell functions might impact the repair mechanisms needed in diabetic patients to protect from vascular complications. Further investigations are required to establish therapeutic targets to improve EPCs repair function.

Type 2 diabetes mullites (T2DM) results in different cardiovascular complications. The main cause of these complications is endothelial dysfunction, which affects the endothelium physiologically and pathologically. The chronic hyperglycemia introduced by T2DM impacts the pivotal enzyme endothelial nitric oxide synthase (eNOS) in terms of phosphorylation and dimerization, which initiates oxidative stress and reduces the bioavailability of the vasodilator nitric oxide. To overcome endothelial dysfunction, endothelial progenitor cells (EPCs) contribute to vascular repair due to their regenerative characteristics. The effects of hyperglycemia on EPCs are understudied. Thus, this study aims to investigate the effects of hyperglycemia on the eNOS/Akt signaling pathway and reactive oxygen species (ROS) formation. Cells were treated with normal glucose (NG, 5.5mM) and high glucose (HG, 25mM) media for 3 & 6 days, and the effect on eNOS and Akt phosphorylation were assessed using western blot. ROS was assessed using CellROX stain following 1 and 3 days of treatment. Results showed that both acute and chronic hyperglycemia showed a trend towards decrease in phosphorylation of eNOS and Akt. In addition, ROS formation was increased following 24hr compared to NG. Further investigations are needed to enhance the capability of BOECs to serve as therapeutic tools in T2DM.