Hyperglycaemia exerts deleterious effects on late endothelial progenitor cell secretion actions

Abstract

Endothelial progenitor cells (EPCs) play a fundamental role in tissue regeneration and vascular repair both by differentiating into endothelial cells and by secretion of vasoactive substances that promote angiogenesis and maintain vascular homeostasis. It has previously been shown that hyperglycaemia impairs early and late EPC functions, such as differentiation, proliferation and adhesion. However, its role in the regulation of the production of vasoactive substances in EPCs, especially in late EPCs, is less well defined. We investigated the effects of hyperglycaemia on the production of vasodilator, fibrinolytic and angiogenic growth factors, and also on the activity of superoxide dismutase (SOD) in late EPCs. For this purpose, late EPCs were incubated with different concentrations of D-glucose (5-40 mmol/L) for 24 hr. Levels of nitric oxide (NO), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), prostaglandin I(2) (PGI(2)), vascular endothelial growth factor (VEGF) and the activity of SOD were measured by enzyme-linked immunosorbent assay (ELISA). Under high glucose stress conditions, late EPCs exhibited lower levels of NO, t-PA, PAI-1, PGI(2) and VEGF compared to control medium (5 mmol/L glucose). Moreover, high glucose was also observed to decrease the activity of SOD in late EPCs. These results suggest that hyperglycaemia-induced impairment of late EPC secretion functions could contribute to the development of vascular disease in diabetes.