Dysfunctional endothelium and vascular progenitors: A legacy of impaired glucose metabolism

Madhulika Dixit, Department of Biotechnology, IIT Madras

Vascular aberrations are triggered prior to the onset of hyperglycemia in diabetic patients. These changes in the vasculature are characterized by endothelial inflammation and decreased bio-availability of nitric oxide during insulin resistance. Compensatory hyperinsulinemia observed during insulin resistance is a potential risk factor for cardiovascular complications. We observed that sustained exposure (up to 48 hours) of human umbilical vein derived endothelial cells (HUVECs) to insulin (1-100nM) enhances the surface expression of cell adhesion molecules and consequent adherence of leukocytes onto the endothelial monolayer. This is due to decrease in intracellular nitric oxide levels, and enhanced expression and activity of protein tyrosine phosphatase SHP2. Decrease in nitric oxide levels is due to inactivation of endothelial nitric oxide synthase (eNOS) and up-regulation of its competitive inhibitor, arginase. The recurrent endothelial damage thus caused is repaired in healthy individuals through trans- differentiation of circulating endothelial progenitors. In two independent studies, we compared the adhesion, migration and endothelial differentiation potential of vascular progenitors from drug naïve healthy and insulin resistant subjects. Intriguingly presence of insulin resistance impaired adhesive and migratory ability of these cells. The talk will highlight the link between impaired glucose metabolism and endothelial health.