Endothelial Progenitor Cell Dysfunction in the Pathogenesis of Vascular Complications of Diabetes

Abstract

Diabetes mellitus, a metabolic disorder characterized by high blood glucose, is one of the main risk factors in the development of vascular complications affecting both large and small blood vessels. A major challenge is the discovery of new mediators and biomarkers for diabetes-related vascular complications. In this regard, accumulating evidence indicate that endothelial progenitor cells (EPCs), derived from the bone marrow and peripheral blood, are critical for the maintenance and regeneration of endothelial cells contributing to repair and restoration of vascular wall integrity. The studies reveal that the reduced number of circulating EPCs under diabetic conditions can predict cardiovascular outcomes, and EPC dysfunction could contribute to the pathogenesis of diabetes - associated vascular disease. This chapter discusses the EPC dysfunction in relationship to vascular complications of diabetes, highlighting the pathophysiology of diabetic vascular complications, mechanisms leading to EPC dysfunction in diabetes and diabetic vascular complications, significance of EPCs in the pathogenesis of vascular complications of diabetes and potential therapeutic implications of EPCs in diabetes-associated vascular complications. In particular, to understand the EPC significance in diabetes, the effects of hyperglycaemia, insulin resistance, insulin like growth factor 1, nitric oxide, oxidative stress, PI3K/Akt signaling pathway, inflammation, and of altered microRNA expression on the EPC dysfunctionality have been considered. A comprehensive knowledge of EPC role in all diabetic complications may help to develop new research strategies to demonstrate and consolidate their clinical relevance so that they become diagnostic biomarkers and pharmacological targets to prevent and treat diabetes-related vascular complications. Increasing the number and functional capacity of EPCs by different approaches may favorably modify the risk for cardiovascular complications and survival for people suffering from diabetes.