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PGC1β activates an antiangiogenic program to repress neoangiogenesis in muscle ischemia

Yadav, Vikas; Matsakas, Antonios; Lorca, Sabina; Narkar, Vihang A.


Vikas Yadav

Antonios Matsakas

Sabina Lorca

Vihang A. Narkar


Revascularization of ischemic skeletalmuscle is governed by a balance between pro- and antiangiogenic factors in multiple cell types but particularly in myocytes and endothelial cells. Whereas the regulators of proangiogenic factors are well defined (e.g.,hypoxia-inducible factor [HIF]), the transcriptional pathways encoding antiangiogenic factors remain unknown. We report that the transcriptional cofactor PGC1β drives an antiangiogenic gene program in muscle and endothelial cells. PGC1β transcriptionally represses proangiogenic genes (e.g., Vegfc, Vegfd, Pdgfb, Angpt1, Angpt2, Fgf1, and Fgf2) and induces antiangiogenic genes (e.g., Thbs1, Thbs2, Angstat, Pedf, and Vash1). Consequently, musclespecific PGC1β overexpression impairs muscle revascularization in ischemia and PGC1β deletion enhances it. PGC1β overexpression or deletion in endothelial cells also blocks or stimulates angiogenesis, respectively. PGC1β stimulates the antiangiogenic genes partly by coactivating COUP-TFI. Furthermore, roangiogenic stimuli such as hypoxia, hypoxia-mimetic agents, and ischemia decrease PGC1β expression in a HIF-dependent manner. PGC1β is an antiangiogenic transcriptional switch that could be targeted for therapeutic angiogenesis.


Yadav, V., Matsakas, A., Lorca, S., & Narkar, V. A. (2014). PGC1β activates an antiangiogenic program to repress neoangiogenesis in muscle ischemia. Cell reports, 8(3), 783-797.

Acceptance Date Jun 20, 2014
Online Publication Date Jul 24, 2014
Publication Date Aug 7, 2014
Deposit Date May 20, 2015
Publicly Available Date Oct 27, 2022
Journal Cell reports
Print ISSN 2211-1247
Electronic ISSN 2211-1247
Publisher Cell Press
Peer Reviewed Peer Reviewed
Volume 8
Issue 3
Pages 783-797
Keywords Neoangiogenesis, Muscle ischemia, PGC1β
Public URL
Publisher URL
Additional Information Copy of article first published in: Cell reports, 2014, v.8, issue 3.


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