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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:698.)
© 2005 American Heart Association, Inc.

Vascular Biology

Hyperglycemia Reduces Survival and Impairs Function of Circulating Blood-Derived Progenitor Cells

Nicolle Kränkel; Volker Adams; Axel Linke; Stephan Gielen; Sandra Erbs; Karsten Lenk; Gerhard Schuler; Rainer Hambrecht

From the Department of Internal Medicine/Cardiology, Heart Center Leipzig, University of Leipzig, Germany.

Correspondence to Rainer Hambrecht, MD, Professor of Medicine, Department of Internal Medicine/Cardiology University of Leipzig, Heart Center, Struempellstr. 39, 04289, Leipzig, Germany. E-mail hamr{at}medizin.uni-leipzig.de

Objective— Function and availability of circulating progenitor cells (CPC) have been shown to be impaired in patients with diabetes mellitus (DM). Therefore, the aim of the present study was to analyze possible mechanisms leading to the reduction of CPC amount and function.

Methods and Results— Peripheral blood mononuclear cells (MNCs) of healthy donors (n=15) were cultivated under hyperglycemia (HG) conditions (12 mmol/L D-Glucose) or in osmotic control medium (Con) (5 mmol/L D-Glucose plus 7 mmol/L L-Glucose) for 7 days. CPC amount was determined by uptake of acetylated low-density lipoprotein and lectin binding. On the functional level, cell cycle status, nitric oxide (NO) production, and migrational and integrative capacity of CPCs were assessed. HG conditions caused a significant decrease in CPC amount derived from healthy MNCs. Furthermore, HG conditions led to a functional impairment, reflected in a decreased NO production and matrix metalloproteinase (MMP)-9 activity, as well as an impairment of the migrational and integrative capacities.

Conclusion— HG, a main feature of DM, affects important functional characteristics of CPCs. These results may provide further insight into the pathomechanism of endothelial dysfunction in HG.

In circulating progenitor cells (CPC), hyperglycemia induces cell-cycle arrest, impaired NO synthesis, and decreased migrational and integrative capacity. These mechanisms might contribute to the decline of CPC amount and function in diabetes mellitus.

Key Words: circulating progenitor cells • endothelium • hyperglycemia • nitric oxide • vascular biology

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