| Peripheral endothelial dysfunction is an important mechanism contributing to exercise intolerance in chronic heart failure (CHF). Recent evidence indicates that efficient repair mechanisms are required to maintain endothelial integrity, a process in which endothelial progenitor cells (EPC) and circulating angiogenic cells (CAC) play a key role.;The aims of the dissertation are the following: (1) to generate insight in the biology of vasculogenic cells in CHF patients, (2) to investigate the effect of a single exercise bout on EPC/CAC in CHF patients and healthy subjects and (3) to evaluate whether a physical training program affects EPC/CAC in CHF patients.;Firstly, we demonstrate that endothelial repair mechanisms are deficient in CHF patients: low numbers of EPC and CAC dysfunction correlate with the degree of endothelial dysfunction and exercise intolerance. Secondly, we show that the number of EPC in the peripheral circulation increases immediately after a maximal exercise bout in healthy subjects. In CHF patients however, this effect is severely attenuated, possibly due to bone marrow exhaustion. On the other hand, a single exercise bout rapidly corrects CAC function, an effect that is more prominent with heart failure progression.;Thirdly, exercise training in CHF reverses CAC dysfunction in the long-term and increases the level of circulating EPC, coinciding with correction of peripheral endothelial function. The acute exercise-induced changes on CAC function wane with exercise training, suggesting that repetitive exercise bouts progressively lead to endothelial repair.;In conclusion, this dissertation provides arguments that physical activity - either acute or repetitive - affects endothelial repair mechanisms that are necessary for the maintenance of endothelial integrity in CHF patients. |
