Abstract 3796: Exercise Training Induces Endogenous Tissue Regeneration in Chronic Heart Failure: Impact on Number and Function of Circulating Progenitor Cells and Skeletal Muscle Neovascularization
Bone marrow-derived stem cells are known to contribute to endogenous tissue regeneration. In patients (pts) with chronic heart failure (CHF) number and function of circulating progenitor cells (CPC) are reduced. This impairment in regenerative capacity is associated with a reduction of capillary density in skeletal muscle in CHF. Aim of the present study was to determine, whether physical exersice training results in an activation and/or functional improvement of CPCs, thereby leading to an neovascularization of skeletal muscle in pts with severe CHF.
Methods: Thirty-seven pts with CHF (LVEF 24 ± 2%, NYHA class IIIb) were randomized to 12 weeks of exercise training (30min bicycle ergometer training at 50 – 60% of peak oxygen uptake/d) or sedentary lifestyle (control). At begin and after 12 weeks, number of circulating CD 34+ stem cells and CD34/KDR+ CPCs were quantified by FACS and functional properties of CPCs were assessed using migration assay. Percutanous biopsies of the vastus lateralis muscle were obtained, the number of CD 34+ cells and capillary density were quantified applying immunohistochemistry.
Results: Twelve weeks of exercise training results in an increase in number of CD34+ stem cells by +47% from 1756 ± 377 to 2589 ± 521 cells/mL blood (p<0.05 vs. begin and control), an augmentation of CD34/KDR+ CPCs by +199% from 164 ± 51 to 327 ± 142 cells/mL blood (p<0.05 vs. begin and control) and an improvement in migratory capacity of CPCs by +149% in the training group (p<0.05 vs. begin and control). This was associated with an increase in capillary density in the skeletal muscle by +17% from 1.49 ± 0.11 to 1.70 ± 0.10 von Willebrand factor positve capillaries/ muscle fibre (p<0.01 vs. begin and control), which was partially the result of an enhanced homing of CD34+ cells in skeletal muscle (from 5.8 ± 0.34 to 7.3 ± 0.32 cells per high-power field), p<0.05 vs. control for the change). All above mentioned parameters remained unchanged in the control group.
Conclusion: In pts with severe CHF, physical exercise training increases the amount of CPCs and improves their functional capacity, thereby promoting neovascularization in the skeletal muscle. Therefore, exercise training might have the therapeutic potential to ameliorate endogenous tissue regeneration in CHF.