The effect of passive movement training on angiogenic factors and capillary growth in human skeletal muscle

The effect of a period of passive movement training on angiogenic factors and capillarization in skeletal muscle was examined. Seven young males were subjected to passive training for 90 min, four times per week in a motor‐driven knee extensor device that extended one knee passively at 80 cycles min−1. The other leg was used as control. Muscle biopsies were obtained from m. v. lateralis of both legs before as well as after 2 and 4 weeks of training. After the training period, passive movement and active exercise were performed with both legs, and muscle interstitial fluid was sampled from microdialysis probes in the thigh. After 2 weeks of training there was a 2‐fold higher level of Ki‐67 positive cells, co‐localized with endothelial cells, in the passively trained leg which was paralleled by an increase in the number of capillaries around a fibre (P < 0.05). Capillary density was higher than pre‐training at 4 weeks of training (P < 0.05). The training induced an increase in the mRNA level of endothelial nitric oxide synthase (eNOS), the angiopoietin receptor Tie‐2 and matrix metalloproteinase (MMP)‐9 in the passively trained leg and MMP‐2 and tissue inhibitor of MMP (TIMP)‐1 mRNA were elevated in both legs. Acute passive movement increased (P < 0.05) muscle interstitial vascular endothelial growth factor (VEGF) levels 4‐ to 6‐fold above rest and the proliferative effect, determined in vitro, of the muscle interstitial fluid ∼16‐fold compared to perfusate. The magnitude of increase was similar for active exercise. The results demonstrate that a period of passive movement promotes endothelial cell proliferation and angiogenic factors and initiates capillarization in skeletal muscle. Exercise training leads to many adaptations in the skeletal muscle that improve its function. One is growth of the smallest blood vessels, capillaries. These allow for oxygen and nutrients carried by the blood to reach the muscle cells. Our intention with this study was to determine whether 90 min of passive movement of the lower leg three times per week for 4 weeks would lead to growth of capillaries in the muscle. The results show that such passive movement of the leg enhances blood flow, stretches the muscle and leads to stimulation of capillary growth. This finding is important for our understanding of what makes capillaries grow and may help patients with cardiovascular disease.