Recent advances and new insights into muscular lymphangiogenesis in health and disease.

The lymphatic vessels have been implicated in maintenance of interstitial fluid homeostasis and immune responses, and pathological conditions including inflammation, wound healing, lymphedema and tumor progression. The knowledge about the lymphatic structure and function in muscles, especially in muscular disorders, remains fragmentary and elusive. LYVE-1-positive initial lymphatics are generally found around skeletal muscle fibers, but not distributed in a fiber type-specific manner. Recent advances in lymphatic research have identified that exercise stimuli trigger adaptive changes in the behavior of initial lymphatics and upregulate lymphangiogenesis. Increasing evidence has supported that muscle disorders are closely correlated with lymphatic dysfunction, growth and remodeling. During these processes, VEGFR-3 and its ligands VEGF-C and VEGF-D are important regulators of muscular lymphangiogenesis. Further studies are necessary to clarify the structural and molecular plasticity of mammalian muscular lymphatics in response to endurance training and pathological events.