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 ECs specific pfkfb3 knockout mice 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 ECs specific pfkfb3 knockout failed to polarized to M2-like macrophages after HLI. Reduced macrophage polarization impairs angiogenesis and muscle regeneration. The RNAseq data are ECs specific pfkfb3 knockout and wild type muscle derived macrophages 3 days after HLI.