O207	Reendothelialization capacity and nitric oxide release of endothelial progenitor cells is impaired in patients with type 2 diabetes: effect of rosiglitazone treatment.
1S.A.Sorrentino, 2F.H.Bahlmann, 1Chr.Besler, 1M.Müller, 1S.Schulz, 1N.Kirchhoff, 2D.Fliser, 1H.Drexler, 1U.Landmesser
1Department of Cardiology and Angiology, Medical School of Hannover, Hannover, DE; 2Department of Nephrology, Medical School of Hannover, Hannover, DE.

Background: Endothelial progenitor cells (EPCs) have been suggested to contribute to reendothelialization after vascular injury, and nitric oxide (NO) may be involved in this process. The present study was designed to compare in vivo reendothelialization capacity of EPCs from patients with diabetes and age- and sex-matched healthy controls, and to evaluate the impact of treatment with the PPARγ agonist rosiglitazone on these processes in diabetics. Methods: In vivo endothelial regeneration capacity of EPCs from diabetics and healthy subjects was determined by transplantation (Tx) of EPC (5x105 cells) into nude mice using a carotid artery endothelial injury model. The reendothelialized area (REA) was assessed 3 days post-Tx by a computer-based morphometric analysis. Moreover, patients with diabetes were randomized to two-week treatment with rosiglitazone (4 mg bid) or placebo. Reendothelialization capacity, NO release and reactive oxygen species (ROS) production of EPCs (assessed by electron spin resonance spectroscopy) were determined. Results: Reendothelialization of carotid arteries was markedly accelerated after transplantation of EPCs from healthy subjects into nude mice as compared to placebo (REA 37±3 vs. 5±0.5%; P<0.01). In vivo reendothelialization capacity of EPCs from diabetic patients was markeldy impaired (REA 8±0.5%; P<0.01 vs. healthy subjects). Rosiglitazone treatment restored reendothelialization capacity of EPCs from diabetic patients (REA rosiglitazone vs. placebo: 36±1 vs. 8±0.5%; p<0.01), increased baseline and stimulated NO production of EPCs and reduced ROS production of EPCs from diabetic patients. Conclusion: Endothelial progenitor cells from healthy subjects substantially accelerate in vivo reendothelialization, while endothelial regeneration capacity is severely impaired in EPCs from diabetic patients. Furthermore, rosiglitazone treatment restores EPC reendothelialization capacity, increases NO production and reduces ROS production of EPCs in patients with type 2 diabetes. These beneficial effects may importantly contribute to vasoprotective effects of rosiglitazone treatment.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.