| First Author | Yadav V | Year | 2014 |
| Journal | Cell Rep | Volume | 8 |
| Issue | 3 | Pages | 783-97 |
| PubMed ID | 25066120 | Mgi Jnum | J:262247 |
| Mgi Id | MGI:6155460 | Doi | 10.1016/j.celrep.2014.06.040 |
| Citation | Yadav V, et al. (2014) PGC1beta activates an antiangiogenic program to repress neoangiogenesis in muscle ischemia. Cell Rep 8(3):783-97 |
| abstractText | Revascularization of ischemic skeletal muscle 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 PGC1beta drives an antiangiogenic gene program in muscle and endothelial cells. PGC1beta 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, muscle-specific PGC1beta overexpression impairs muscle revascularization in ischemia and PGC1beta deletion enhances it. PGC1beta overexpression or deletion in endothelial cells also blocks or stimulates angiogenesis, respectively. PGC1beta stimulates the antiangiogenic genes partly by coactivating COUP-TFI. Furthermore, proangiogenic stimuli such as hypoxia, hypoxia-mimetic agents, and ischemia decrease PGC1beta expression in a HIF-dependent manner. PGC1beta is an antiangiogenic transcriptional switch that could be targeted for therapeutic angiogenesis. |
