Monday, 1 September 2008 - European Heart Journal

260 Healthy bone marrow for a healthy heart
MI and left ventricular dysfunction. This may contribute to a better outcome after
acute event.
1632 Vascular oxidative stress inhibits mobilization of
circulating stem cells with endothelial progenitor
capacity in mice
T. Suvorava1 ,S.Kumpf1 ,V.Adams2 ,G.Kojda1 . 1Heinrich Heine
University, Institute of Pharmacology, Duesseldorf, Germany;
2University of Leipzig, Heart Center Leipzig, Leipzig, Germany
Purpose: The number of circulating stem cells with endothelial progenitor capacity
(EPCs) was reported to inversely correlate with the number of cardiovascular
risk factors and is reduced in cardiovascular disease. Despite recent advances
in EPC studies, the molecular mechanisms of EPC mobilization remain unclear.
We sought to investigate the effects of increased vascular oxidative stress on
exercise-induced EPCs mobilization.
Methods: Transgenic mice with a vascular-specific overexpression of catalase
and reduced vascular levels of oxidative stress (cat++) and their transgene negative
littermates (catn) were assigned to a sedentary group and a group undergoing
moderate forced exercise training (15 m/min, 30 min, 5 days a week, 3
weeks). The number of EPCs in peripheral blood was measured by Fluorescence-
Activated Cell Sorting (FACS) using anti-mouse CD3, Flk-1 and CD34, CD133 or
Sca-1 antibodies. Additionally, the effects of different amounts of physical activity
on EPC mobilization were investigated in sedentary (singularized), freely moving
(6 mice per cage), voluntary (9.8±0.7 km/night) and forced (15 m/min, 5 days, 30
min/day) running C57BL/6 mice.
Results: There was no difference in circulating EPCs between sedentary and
freely moving C57BL/6 mice (p>0.05, n=5). Three weeks of forced exercise training
failed to mobilize EPCs defined as double positive for Flk-1 and CD34 or more
immature hematopoeitic stem marker CD133 (p>0.05, n=5-9). Similarly, the number
of EPCs was not different between sedentary and voluntary exercised groups
(n=5-8, all p>0.05). FACS analysis of cat++ and catn peripheral blood revealed no
effect of catalase overexpression on the basal level of circulating EPCs (p=0.68,
n=8). Inhibition of catalase by 3 week treatment with catalase inhibitor aminotriazole
(670 mg/kg in drinking water) strongly reduced the number of endothelial progenitors
in blood of sedentary catn, and to a lesser extend also in cat++(p