Skeletal Muscle-Resident Pericyte Responses to Conditions of Use and Disuse

Skeletal muscle structure and function are dependent on the presence or absence of mechanical cues in the tissue microenvironment. High intensity or sustained contractions can build muscle mass with exercise training, whereas bedrest or limb immobilization result in loss of muscle mass. Molecular signaling pathways, such as mTORC1 and induction of activating transcription factor 4 (ATF4), regulate intrinsic myofiber growth and atrophy respectively, yet the extent to which mononuclear cells outside the fiber contribute to muscle structure remodeling remains unclear. The skeletal muscle microenvironment is enriched with mononuclear cells, including progenitor and stem cells, fibroblasts, immune cells, and vascular stromal cells. All possess the potential to sense mechanical cues and contribute to structural remodeling, but the intricate positioning of vascular stromal cells around vessels make these cells particularly receptive to changes in mechanical stimuli due to alterations in both blood perfusion and contraction. Recent studies suggest that pericytes, a population of vascular stromal cells supporting capillaries and venules, are highly responsive to conditions of use and disuse. This chapter discusses the characteristics and behavior of skeletal muscle-derived pericytes as well as the specific responses to physiological stimuli with which muscle can be subjected. Determining how pericytes behave in situations of muscle activation and immobilization is important for the development of cell-based therapies for the treatment of skeletal muscle disorders.