| First Author | Sawada N | Year | 2014 |
| Journal | Cell Metab | Volume | 19 |
| Issue | 2 | Pages | 246-58 |
| PubMed ID | 24506866 | Mgi Jnum | J:210653 |
| Mgi Id | MGI:5571567 | Doi | 10.1016/j.cmet.2013.12.014 |
| Citation | Sawada N, et al. (2014) Endothelial PGC-1alpha mediates vascular dysfunction in diabetes. Cell Metab 19(2):246-58 |
| abstractText | Endothelial dysfunction is a central hallmark of diabetes. The transcriptional coactivator PGC-1alpha is a powerful regulator of metabolism, but its role in endothelial cells remains poorly understood. We show here that endothelial PGC-1alpha expression is high in diabetic rodents and humans and that PGC-1alpha powerfully blocks endothelial migration in cell culture and vasculogenesis in vivo. Mechanistically, PGC-1alpha induces Notch signaling, blunts activation of Rac/Akt/eNOS signaling, and renders endothelial cells unresponsive to established angiogenic factors. Transgenic overexpression of PGC-1alpha in the endothelium mimics multiple diabetic phenotypes, including aberrant re-endothelialization after carotid injury, blunted wound healing, and reduced blood flow recovery after hindlimb ischemia. Conversely, deletion of endothelial PGC-1alpha rescues the blunted wound healing and recovery from hindlimb ischemia seen in type 1 and type 2 diabetes. Endothelial PGC-1alpha thus potently inhibits endothelial function and angiogenesis, and induction of endothelial PGC-1alpha contributes to multiple aspects of vascular dysfunction in diabetes. |
