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Control of endothelial function and angiogenesis by PGC1-α

AutorMonsalve, María
Fecha de publicación2014
CitaciónGEIRLI 2014
Resumen[Rationale]: Peroxisome proliferator activated receptor gco-activator 1α(PGC-1α) is a regulator of oxidative metabolism. Endothelial cell migration requires the downregulation of PGC-1α, suggesting that PGC-1α could play a role in angiogeneis. [Objective]: This study aims to evaluate the relevance of endothelial PGC-1ain angiogenesis. [Methods and results]: Endothelial cells (ECs) from mice deleted for expression of PGC-1α show reduced adhesion to the extracellular matrix, slower spreading, poor formation of cellular junctions, and a disorganized cytoskeleton and random motility, with enhanced tip phenotype and a poor response to Vascular endothelial growth factor-A (VEGF-A). In vivo, deletion of PGC-1α results in a reduced retinal vascular density and poor pericyte coverage. PGC-1α deleted mice exposed to hyperoxia during retinal vascular development exhibit exacerbated vascular abnormalities, including extensive hemorrhage, highly unstructured areas and very poor perfusion compared with wild-type mice. Structural analysis showed reduction of endothelial VE-cadherin, suggesting defective inter-cellular junctions. Interenstingly, this phenotype is partially reversed by antioxidant administration, suggesting that elevated production of mitochondrial reactive oxygen species (ROS) in the absence of PGC-1α is functionally important. Finally, in vitro studies show that antioxidant treatment improves VEGF-A signaling, suggesting the toxic effect of ROS may be caused by the alteration of the VEGF-A signaling pathway. [Conclusions]: Our findings indicate that PGC-1α plays a role in the control of de novo angiogenesis, and its absence results in a poor vascular stability.
DescripciónResumen del trabajo presentado al X Meeting of the Spanish Group for Research on Free Radicals (GEIRLI): "Symposium on Oxidative Stress and Redox Signaling in Biology and Medicine"; homage to Luis Alfonso del Río and Pere Puig-Parellada, celebrado del 2 al 4 de junio de 2014 en la Facultad de Medicina de la Universidad de Valencia.
URIhttp://hdl.handle.net/10261/152364
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