Modulation of vascular endothelial gene expression by physical training in patients with chronic heart failure.
BACKGROUND: Abnormalities of the skeletal muscle vasculature, such as endothelial dysfunction and reduced microvascular density, can be reversed by physical training in patients with chronic heart failure. The molecular mechanisms that mediate the beneficial effects of physical training on the vascular endothelium are unknown. METHODS: Endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) gene expression in the skeletal muscle, peak oxygen consumption (VO2) and calf peak reactive hyperemia were measured before and after 12 weeks of supervised physical training in 10 patients with chronic heart failure. Five patients with heart failure of similar severity who did not participate in the training program served as controls. RESULTS: The effects of physical training on eNOS and VEGF gene expression were heterogeneous. eNOS gene expression increased 3-4 fold in 4 patients while it remained constant in 6 patients. VEGF gene expression increased significantly in all patients who were not treated with beta-adrenergic blockade and remained constant in all patients who were treated with beta-adrenergic blockade. In contrast, physical training increased peak VO2 and calf peak reactive hyperemia in all patients. Mean peak VO2 increased from 13.13 +/- 2.21 to 16.19 +/- 2.69 ml/kg/min (p < 0.001) and calf peak reactive hyperemia increased from 19.7 +/- 2.3 to 29.6 +/- 4.0 ml*min(-1)*100 ml(-1) (p < 0.001). CONCLUSIONS: A supervised program of physical training that consistently enhanced peak VO2 and vascular reactivity in patients with chronic heart failure increased or left eNOS and VEGF gene expression unchanged in skeletal muscle. Changes in vascular endothelial gene expression may contribute to the benefits of training on vascular endothelial function but are not solely responsible for these benefits.