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Diabetes 53:195-199, 2004
© 2004 by the American Diabetes Association, Inc.

Endothelial Progenitor Cell Dysfunction

A Novel Concept in the Pathogenesis of Vascular Complications of Type 1 Diabetes

Cindy J.M. Loomans1, Eelco J.P. de Koning1, Frank J.T. Staal2, Maarten B. Rookmaaker1, Caroline Verseyden1, Hetty C. de Boer1, Marianne C. Verhaar1, Branko Braam3, Ton J. Rabelink1, and Anton-Jan van Zonneveld1

1 Department of Vascular Medicine and Diabetology, University Medical Center Utrecht, Utrecht, the Netherlands
2 Department of Immunology, Erasmus Medical Center, Rotterdam, the Netherlands
3 Department of Nephology, University Medical Center Utrecht, Utrecht, the Netherlands

Type 1 diabetes is associated with reduced vascular repair, as indicated by impaired wound healing and reduced collateral formation in ischemia. Recently, endothelial progenitor cells (EPCs) have been identified as important regulators of these processes. We therefore explored the concept that EPCs are dysfunctional in diabetes. The number of EPCs obtained from type 1 diabetic patients in culture was 44% lower compared with age- and sex-matched control subjects (P < 0.001). This reduction was inversely related to levels of HbA1c (R = -0.68, P = 0.01). In addition, we demonstrated that patient EPCs were also impaired in function using an in vitro angiogenesis assay. Conditioned media from patient EPCs were significantly reduced in their capacity to support endothelial tube formation in comparison to control EPCs. Therefore, despite culturing the EPCs under normoglycemic conditions, functional differences between patient and control EPCs were maintained. Our findings demonstrate that adverse metabolic stress factors in type 1 diabetes are associated with reduced EPC numbers and angiogenicity. We hypothesize that EPC dysfunction contributes to the pathogenesis of vascular complications in type 1 diabetes.

Address correspondence and reprint requests to Anton-Jan van Zonneveld, PhD, Department of Vascular Medicine, University Medical Center Utrecht, G02.402, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands. E-mail: a.j.vanzonneveld{at}azu.nl


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Copyright © 2004 by the American Diabetes Association.