Abstract 3797: Physical Exercise Training Promotes Proliferation and Differentiation of Endogenous Progenitor Cells in the Skeletal Muscle of Patients With Chronic Heart Failure
Exercise training (ET) partially corrects alterations of the skeletal muscle (SM) in patients (Pts) with chronic heart failure (CHF) but the mechanisms are only partially understood. Recently, a population of endogenous progenitor cells - which has a remarkable capacity to regenerate damaged tissue - was discovered in the SM. Aim of the present study was to determine, whether ET activates c-kit+ progenitor cells in the SM and thereby contributes to endogenous muscle repair in patients with CHF.
Methods: Pts with CHF (NYHA class II to III b, LVEF 25 ± 2 %) were randomised to 6 months of exercise training (T, n=25) or an inactive control group (C, n=25). The number of c-kit+ cells was determined by immunohistochemistry in SM biopsies obtained in all patients of C and T at begin (B) and at 6 months of follow-up (FU), and in 30 age-matched healthy subjects without any cardiovascular disease (LVEF 69 ± 5 %). Myocyte-lineage commitment of c-kit+ cells was identified by the co-expression of “myocyte enhancer factor 2”, cycling c-kit+ cells were recognized by the co-expression of the proliferation marker Ki67 applying immunohistochemistry.
Results: In CHF, the number of c-kit+ cells, c-kit/MEF2+ cells and proliferating c-kit/Ki67+ cells in the SM was reduced by 70 %, 63 %, and 65 %, respectively as compared to healthy subjects (p<0.05). There was a close correlation between c-kit+ progenitor cell count and SM cross sectional area determined by computed tomography (r=0.67, p<0.05). Exercise training increased the amount of c-kit+ cells in the SM by 109 % from 44 ± 12 (B) to 92 ± 27 cells/cm2 SM tissue (FU) (p<0.05) in CHF. Moreover, the number of c-kit/MEF2+ cells expanded by 166 % from 12 ± 5 at B to 32 ± 11 cells/cm2 SM tissue at FU (p<0.05) as a result of the training intervention. Additionally, ET enlarged the population of c-kit/Ki67+ cells 6fold (from 3 ± 2 cells/cm2 at B to 19 ± 7 cells/cm2 at FU (p<0.05). All of the parameters remained unchanged in C.
Conclusion: The altered functional capacity of endogenous c-kit+ cells might partially explain SM dysfunction in CHF. Exercise training increases the number of c-kit+ progenitor cells, augments proliferation as well as differentiation of those cells in the SM and, thereby, might induce skeletal muscle regeneration in patients with CHF.