Hellsten Ylva, Hoier Birgitte
*Department of Nutrition, Exercise and Sports, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark.
Biochem Soc Trans. 2014 Dec;42(6):1616-22. doi: 10.1042/BST20140197.
In human skeletal muscle, the capillary net readily adapts according to the level of muscular activity to allow for optimal diffusion conditions for oxygen from the blood to the muscle. Animal studies have demonstrated that stimulation of capillary growth in skeletal muscle can occur either by mechanical or by chemical signalling. Mechanical signals originate from shear stress forces on the endothelial cell layer induced by the blood flowing through the vessel, but include also mechanical stretch and compression of the vascular structures and the surrounding tissue, as the muscle contracts. Depending on the mechanical signal provided, capillary growth may occur either by longitudinal splitting (shear stress) or by sprouting (passive stretch). The mechanical signals initiate angiogenic processes by up-regulation or release of angioregulatory proteins that either promote, modulate or inhibit angiogenesis. A number of such regulatory proteins have been described in skeletal muscle in animal and cell models but also in human skeletal muscle. Important pro-angiogenic factors in skeletal muscle are vascular endothelial growth factor, endothelial nitric oxide synthase and angiopoietin 2, whereas angiostatic factors include thrombospondin-1 and tissue inhibitor of matrix metalloproteinase. Which of these angiogenic factors are up-regulated in the muscle tissue depends on the mechanical and chemical stimulus provided and, consequently, the process by which capillary growth occurs. The present review addresses physiological signals and angiogenic factors in skeletal muscle with a focus on human data.
在人类骨骼肌中，毛细血管网会根据肌肉活动水平迅速适应，以确保氧气从血液到肌肉的扩散条件达到最佳。动物研究表明，骨骼肌中毛细血管的生长可以通过机械信号或化学信号来刺激。机械信号源于血液流经血管时在内皮细胞层上产生的剪切应力，但也包括肌肉收缩时血管结构和周围组织受到的机械拉伸和压缩。根据所提供的机械信号，毛细血管的生长可能通过纵向分裂（剪切应力）或出芽（被动拉伸）发生。机械信号通过上调或释放血管调节蛋白来启动血管生成过程，这些蛋白可促进、调节或抑制血管生成。在动物和细胞模型以及人类骨骼肌中，已经描述了许多此类调节蛋白。骨骼肌中重要的促血管生成因子包括血管内皮生长因子、内皮型一氧化氮合酶和血管生成素2，而血管生成抑制因子包括血小板反应蛋白-1和基质金属蛋白酶组织抑制剂。肌肉组织中哪些血管生成因子会上调取决于所提供的机械和化学刺激，进而取决于毛细血管生长发生的过程。本综述重点关注人类数据，探讨骨骼肌中的生理信号和血管生成因子。
