Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization.

Details

Serval ID
serval:BIB_9417B6A184AC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization.
Journal
Cell metabolism
Author(s)
Zhang J., Muri J., Fitzgerald G., Gorski T., Gianni-Barrera R., Masschelein E., D'Hulst G., Gilardoni P., Turiel G., Fan Z., Wang T., Planque M., Carmeliet P., Pellerin L., Wolfrum C., Fendt S.M., Banfi A., Stockmann C., Soro-Arnáiz I., Kopf M., De Bock K.
ISSN
1932-7420 (Electronic)
ISSN-L
1550-4131
Publication state
Published
Issued date
02/06/2020
Peer-reviewed
Oui
Volume
31
Number
6
Pages
1136-1153.e7
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Endothelial cell (EC)-derived signals contribute to organ regeneration, but angiocrine metabolic communication is not described. We found that EC-specific loss of the glycolytic regulator pfkfb3 reduced ischemic hindlimb revascularization and impaired muscle regeneration. This was caused by the reduced ability of macrophages to adopt a proangiogenic and proregenerative M2-like phenotype. Mechanistically, loss of pfkfb3 reduced lactate secretion by ECs and lowered lactate levels in the ischemic muscle. Addition of lactate to pfkfb3-deficient ECs restored M2-like polarization in an MCT1-dependent fashion. Lactate shuttling by ECs enabled macrophages to promote proliferation and fusion of muscle progenitors. Moreover, VEGF production by lactate-polarized macrophages was increased, resulting in a positive feedback loop that further stimulated angiogenesis. Finally, increasing lactate levels during ischemia rescued macrophage polarization and improved muscle reperfusion and regeneration, whereas macrophage-specific mct1 deletion prevented M2-like polarization. In summary, ECs exploit glycolysis for angiocrine lactate shuttling to steer muscle regeneration from ischemia.
Keywords
MCT1, angiogenesis, angriocrine signals, endothelial cells, ischemia, lactate, macrophage polarization, metabolism, muscle regeneration
Pubmed
Open Access
Yes
Create date
10/06/2020 19:59
Last modification date
31/07/2020 5:26
Usage data