Abstract 5046: Nitric Oxide and Superoxide Dismutase Modulate Endothelial Progenitor Cell Function in Type 2 Diabetes Mellitus
Objectives: To investigate the roles of NO and SOD in glucose-stressed endothelial progenitor cells (EPCs).
Background: The function of EPCs, which are key cells in vascular repair, is impaired in diabetes mellitus (DM). Nitric oxide (NO) and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD), the enzyme that neutralizes superoxide anion (O2−).
Methods: The functions of circulating EPCs from patients with type 2 DM were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O2− generation, NO production, SOD activity, and their ability to form colonies.
Results: EPCs from DM patients generated more O2−, had higher SOD activity, but lower NO bioavailability, than those from the healthy individuals. Serum fasting glucose and HbA1c levels in the DM patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O2− generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucose-stressed EPCs increased NO production, but did not change O2− generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment.
Conclusions: Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 DM patients.