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Vascular oxidative stress inhibits mobilization of circulating stem cells with endothelial progenitor capacity in mice. We sought to investigate the effects of increased vascular oxidative stress on exercise-induced endothelial progenitor capacity (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 using anti-mouse CD3, Flk-1 and CD34, CD133 or Sca-1 antibodies. 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 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 2 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<0.05, n=5-8). When mice with vascular specific overexpression of catalase were subjected to the forced exercise training, the number of circulating EPCs was strongly increased (n=4-8, p<0.05). Furthermore, exercise-induced increase of circulating EPCs was completely abolished in cat++ treated with aminotriazole. Conclusion: Hydrogen peroxide, an important component of vascular oxidative stress inhibits exercise-induced mobilization of EPCs. |
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