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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3591-3597.
Prepublished online as a Blood First Edition Paper on May 25, 2004; DOI 10.1182/blood-2003-12-4103.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Antioxidative stress–associated genes in circulating progenitor cells: evidence for enhanced resistance against oxidative stress

Elisabeth Dernbach, Carmen Urbich, Ralf P. Brandes, Wolf K. Hofmann, Andreas M. Zeiher, and Stefanie Dimmeler

From the Division of Molecular Cardiology, Department of Internal Medicine IV, the Department of Cardiovascular Physiology, and the Department of Hematology and Oncology, Internal Medicine III, University of Frankfurt, Theodor-Stern-Kai 7, Frankfurt, Germany.

Adult and embryonic stem cells hold great promise for regenerative medicine. Expression profiling of stem cells revealed a characteristic imprint of genes, so-called "stemness" genes, providing resistance to stress. Circulating progenitor cells with an endothelial phenotype (EPCs) can be isolated from peripheral blood and contribute to neovascularization and endothelial regeneration. We investigated whether EPCs are equipped with an antioxidative defense to provide resistance against oxidative stress. EPCs exhibited a significantly lower basal reactive oxygen species (ROS) concentration as compared with mature umbilical vein endothelial cells (HUVECs). Incubation with H2O2 (500 µM) or the redox cycler LY-83583 (10 µM) profoundly increased the ROS concentration to 3- and 4-fold and induced apoptosis in HUVECs. In contrast, H2O2 and LY-83583 induced only a minor increase in intracellular ROS levels and apoptosis in EPCs. Consistently, the expression of the intracellular antioxidative enzymes catalase, glutathione peroxidase and manganese superoxide dismutase (MnSOD), was significantly higher in EPCs versus HUVECs and human microvascular endothelial cells. In accordance, combined inhibition of these antioxidative enzymes increased ROS levels in EPCs and impaired EPC survival and migration. Taken together, EPCs reveal a higher expression of antioxidative enzymes and, thus, are exquisitely equipped to be protected against oxidative stress consistent with their progenitor cell character.


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