Endothelial cells control muscle regeneration through angiocrine lactate

We studied metabolic angiocrine mechanisms by which endothelial cell_ECs_ can contribute to muscle regeneration from ischemia by using endothelial specific pfkfb3 knockout mice_pfkfb3DEC_ after hind-limb ischemia_HLI_. During muscle regeneration, monocytes are recruited to the injured area and rapidly become macrophages which initially exhibit a more pro-inflammatory M1-like phenotype but soon thereafter functionally repolarize towards an M2-like phenotype to actively support muscle regeneration. Interestingly, macrophages derived from pfkfb3DEC failed to polarized to M2-like macrophages after HLI. Reduced macrophage polarization impairs angiogenesis and muscle regeneration. The RNAseq data are pfkfb3DEC and pfkfb3WT muscle derived macrophages 3 days after HLI. pfkfb3EC and pfkfb3WT muscle derived macrophages 3 days after HLI.