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

Abstract 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/week in a motor-driven knee extensor device that extended one knee passively at 80 cycles/min. 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 wks 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 VEGF levels 4-6 -fold above rest and the proliferative effect, determined in vitro, of the muscle interstitial fluid ~16-fold compared to perfusate. These increases were similar for active exercise. The results demonstrate that a period of passive movement promotes endothelial cell proliferation, angiogenic factors and initiates capillarization in skeletal muscle. Key words: angiogenesis, passive movement, shear stress, passive stretch, skeletal muscle, microdialysis.