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Título: | Regulation of endothelial function and angiogenesis by PGC-1α relies on ROS control of vascular stability |
Autor: | García-Quintans, Nieves CSIC ORCID; Sánchez-Ramos, Cristina CSIC ORCID; Tierrez, Albert; Olmos, Yolanda CSIC ORCID; Luque, Alfonso; Arza, Elvira; Alfranca, Arántzazu; Redondo, Juan Miguel CSIC ORCID; Monsalve, María CSIC ORCID | Fecha de publicación: | 2015 | Citación: | XXXVIII Congreso de la SEBBM (2015) | Resumen: | [Background]: Peroxisome proliferator activated receptor g co-activator 1a (PGC-1a) is a regulator of mitochondrial oxidative metabolism and reactive oxygen species (ROS) homeostasis that has been show to play a relevant role in angiogenesis. This study aims to investigate the role of ROS homeostasis on the regulation by PGC-1a of angiogenesis. [Methods and results]: We found that endothelial cells (ECs) from mice deleted for PGC-1a display attenuated adhesion to the extracellular matrix, together with slower spreading, reduced formation of cellular junctions, a disorganized cytoskeleton and random motility, and a enhanced tip phenotype. Additionally, PGC-1a-deleted ECs exhibit an altered response to vascular endothelial growth factor-A (VEGF-A). In vivo, deletion of PGC-1a results in reduced pericyte coverage, a de-structured vascular plexus, and low perfusion. Exposure of PGC-1a-/- mice to hyperoxia during retinal vascular development exacerbates these vascular abnormalities. Mice show extensive retinal hemorrhaging and highly unstructured areas compared with wild-type mice. Structural analysis demonstrates a reduction of membrane bound VE-cadherin, suggesting defective inter-cellular junctions. Interestingly, PGC-1a-/- retinas and ECs show a constitutive activation of the VEGF-A signaling pathway and a poor response to VEGF-A stimulation. This phenotype is partially reversed both in vitro and in vivo by antioxidant administration, indicating that elevated production of mitochondrial ROS in the absence of PGC-1a is a key factor in the alteration of the VEGF-A signaling pathway. [Conclusions]: In summary, our fi ndings indicate that PGC-1a control of ROS homeostasis plays an important role in the control of de novo angiogenesis, and is required for vascular stability. | Descripción: | Resumen del póster presentado al XXXVIII Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Valencia del 7 al 10 de septiembre de 2015. | URI: | http://hdl.handle.net/10261/152372 |
Aparece en las colecciones: | (IIBM) Comunicaciones congresos |
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