Exercise training restores the endothelial response to vascular growth factors in patients with stable coronary artery disease.

Objective: Exercise training partially corrects endothelial dysfunction in patients with coronary artery disease (CAD). Growth factors like vascular endothelial growth factor (VEGF) as well as erythropoietin (EPO) are known to modulate the bioavailability of nitric oxide and, thereby, contribute to the maintenance of a normal vascular tone. The aim of the present study was to determine the impact of 4 weeks of exercise training on circulating growth factors and to elucidate their involvement in the training-induced changes in vasomotion in patients with CAD.

Methods And Results: A total of 39 patients were enrolled (training group: n = 20; control group: n = 19). At start of study and after 4 weeks, average peak flow velocity (APV) of the left internal mammary artery (LIMA) in response to acetylcholine was measured invasively in the treatment and control groups. Serum concentrations of VEGF and EPO were determined by enzyme-linked immunosorbent assay. After exercise training, LIMA APV in response to acetylcholine was increased by 93% (from 69 ± 17% at start of study to 133 ± 16% at 4 weeks, p < 0.01 vs. start of study and control). At start of study, there was no association between any of the vascular growth factors and endothelial function. However, after exercise training a close correlation was apparent between the acetylcholine-induced change in APV and EPO (r = 0.69, p < 0.01) and VEGF (r = 0.76, p < 0.01) serum concentrations. In the control group, these correlations were not evident and there was no change in endothelial function either.

Conclusion: Exercise training improves agonist-mediated endothelium-dependent vasodilatation in CAD, partially through a restoration of the endothelial response to EPO and VEGF.