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Cited by 533

The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index.

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

Open access
Zhang, Jing, Muri, Jonathan, Fitzgerald, Gillian, Gorski, Tatiane, Gianni-Barrera, Roberto, Masschelein, Evi, D’Hulst, Gommaar, Gilardoni, Paola, Turiel, Guillermo, Fan, Zheng, Wang, TongTong, Planque, Mélanie, Carmeliet, Peter, Pellerin, Luc, Wolfrum, Christian, Fendt, Sarah-Maria, Banfi, Andrea, Stockmann, Christian, Soro-Arnáiz, Inés, Kopf, Manfred, De Bock, Katrien·2020·Cell Metabolism

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.

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Metadata

Authors
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.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2020-06
Volume
31
Issue
6
Pages
1136-1153.e7
ISSN
1550-4131 (ISSN-L)
OpenAlex
W3031352795
Cited by
533
References
79
FWCI
14.38
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization. https://app.cochat.ai/papers/10.1016/j.cmet.2020.05.004
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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., . . . De Bock, K. (2020). Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization. Cell Metabolism. https://doi.org/10.1016/j.cmet.2020.05.004

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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