2014 年 3 巻 5 号 p. 483-491
A muscle capillary network is composed of capillaries and anastomoses, and can be modulated under varying conditions. Although exercise induces growth in the capillary network in healthy individuals, physical deconditioning and diabetes cause regression in the capillary network of skeletal muscle. Vascular endothelial growth factor (VEGF) is a critical factor in maintaining the capillary network in skeletal muscle. In addition, the angiopoietin system, is a second family of essential growth factors, that has been identified. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are important angiogenic factors that bind to their common receptor Tie-2 and assist in vascular development and remodeling. Recent studies have demonstrated the contribution of anti-angiogenic factors in controlling angiogenesis in skeletal muscle. Thrombospondin-1 (TSP-1) was shown to be an angiogenesis inhibitor. A balance between pro- and anti-angiogenic factors tightly modulates capillary regression or growth. A chronic decrease in loading and activity resulted in a regression in the capillary network. We have recently shown that the levels of Ang-1 were lower, while levels of Ang-2 were unaffected in atrophied skeletal muscle. Accordingly, the Ang-2/Ang-1 ratio was higher. In addition, the VEGF/TSP-1 ratio was lower. Thus, capillary regression and growth are associated with complex pro- and anti-angiogenic factors in skeletal muscle. Meanwhile, exercise prevents capillary regression associated with a balance between pro- and anti-angiogenic factors in impaired skeletal muscle. Our study provided clear evidence of reduced oxidative enzyme activity levels and capillary regression in skeletal muscle of diabetes. Therefore, exercise has high potential for preventing capillary regression in impaired muscle.