Endothelial progenitor cell dysfunction in diabetes mellitus

Postnatally, Endothelial Progenitor Cells are needed to maintain the integrity of the endothelium (re-endothelialization) and to augment wound healing or vascularize hypoxic areas (neovascularization). Complex networks of different signals and regulators have been identified to be involved in these processes, but exact mechanisms are not completely understood. Unraveling these complex systems however would be beneficial for treatment of vascular disease. In this thesis we focus on different aspects of EPC biology. We look at the nature of these progenitor cells in a normal environment but we also look at the possible role of EPC in the pathogenesis of vascular disease in patients with Diabetes Mellitus. In both a hyperglycemic mouse model and diabetes patients we observe a reduction in circulating numbers of EPC that showed a significant inverse correlation with glycemic control. Not only did we see less EPC, we also found dysfunction of these EPC. We focus further on this dysfunction and describe mechanisms possibly involved as well as drug treatments to (partially) overcome these unfavorable effects of hyperglycemia on EPC. Eventually, we hope that these new insights in EPC dysfunction may contribute to new treatment strategies or even prevention strategies for the treatment of vascular disease in Diabetes patients