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Among these cell types, endothelial cells play a central role not only by regulating blood and nutrient flow to support metabolic and regenerative needs, but also by directly interacting with muscle stem cells and fibro-adipogenic progenitors to regulate stem cell quiescence or activation, and muscle tissue remodeling during its regeneration and growth. The current review article provides a broad overview of the crucial role of the endothelial cells during muscle health and growth, their expansion and interaction with key muscle cell types, governing signaling pathways, and their role in metabolism. Furthermore, we discuss the role of endothelial dysfunction as a pathogenic mechanism in muscular dystrophies, diabetes, peripheral artery disease, and sarcopenia. 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