Contribution of endothelial Piezo1 in mechanically induced muscle hypertrophy

Piezo1 proteins form nonselective cation channels with key roles in endothelial responses to mechanical forces. Here we reveal that endothelial Piezo1 regulates skeletal muscle hypertrophy following mechanical overload. Using a conditional endothelial cell-specific deletion of Piezo1 in adult mice, we assessed the role of endothelial Piezo1 in mechanical overload-induced muscle hypertrophy in the extensor digitorum longus. Endothelial Piezo1 deletion blunted muscle hypertrophy following mechanical overload despite normal baseline vascularisation, as evidenced by a lack of increase in muscle mass and abolished myofibre growth. Despite being required for optimal muscle growth, endothelial Piezo1 was dispensable for muscle regeneration after injury. In line with this, the reduced muscle growth following mechanical overload was not associated with impaired myonuclear accretion. We suggest that endothelial Piezo1 participates in a myofibre partnership that regulates skeletal muscle growth in response to mechanical overload.