Exercise Acutely Reverses Dysfunction of Circulating Angiogenic Cells in Chronic Heart Failure

Aims: Recruitment of endothelial progenitor cells (EPCs) and enhanced activity of circulating angiogenic cells (CACs) might explain the benefits of exercise training in reversing endothelial dysfunction in chronic heart failure (CHF) patients. We studied baseline EPC numbers and CAC function and the effect of a single exercise bout.

Methods And Results: Forty-one CHF patients (mild, n = 22; severe, n = 19) and 13 healthy subjects were included. Migratory activity of CACs was evaluated in vitro and circulating CD34+ and CD34+/KDR+ (EPC) cells were quantified by flow cytometry before and after cardiopulmonary exercise testing (CPET). Circulating stromal cell-derived factor-1alpha (SDF-1alpha) and vascular endothelial growth factor (VEGF) concentrations were measured. Both CAC migration as well as CD34+ cell numbers were significantly reduced in CHF, whereas CD34+/KDR+ cells were not different from controls. Endothelial dysfunction was related to impaired CAC migration (r = 0.318, P = 0.023). Cardiopulmonary exercise testing improved CAC migration in severe (+52%, P < 0.005) and mild CHF (+31%, P < 0.005), restoring it to levels similar to controls. Following CPET, SDF-1alpha increased in healthy controls and mild CHF (P < 0.005). Vascular endothelial growth factor, CD34+, and CD34+/KDR+ cell numbers remained unchanged.

Conclusion: The present findings reveal a potent stimulus of acute exercise to reverse CAC dysfunction in CHF patients with endothelial dysfunction.