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oai:repisalud.isciii.es:20.500.12105/173932024-09-27T09:24:29Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc García-Quintans, Nieves author Sánchez-Ramos, Cristina author Prieto, Ignacio author Tierrez, Alberto author Arza, Elvira author Alfranca, Arantzazu author Redondo, Juan Miguel author Monsalve, María author 2016-04 Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) is a regulator of mitochondrial oxidative metabolism and reactive oxygen species (ROS) homeostasis that is known to be inactivated in diabetic subjects. This study aimed to investigate the contribution of PGC-1α inactivation to the development of oxygen-induced retinopathy. We analyzed retinal vascular development in PGC-1α(-/-) mice. Retinal vasculature of PGC-1α(-/-) mice showed reduced pericyte coverage, a de-structured vascular plexus, and low perfusion. Exposure of PGC-1α(-/-) mice to hyperoxia during retinal vascular development exacerbated these vascular abnormalities, with extensive retinal hemorrhaging and highly unstructured areas as compared with wild-type mice. Structural analysis demonstrated a reduction in membrane-bound VE-cadherin, which was suggestive of defective intercellular junctions. Interestingly, PGC-1α(-/-) retinas showed a constitutive activation of the VEGF-A signaling pathway. This phenotype could be partially reversed by antioxidant administration, indicating that elevated production of ROS in the absence of PGC-1α could be a relevant factor in the alteration of the VEGF-A signaling pathway. Collectively, our findings suggest that PGC-1α control of ROS homeostasis plays an important role in the regulation of de novo angiogenesis and is required for vascular stability. Angiogenesis. 2016 Apr;19(2):217-28. 10.1007/s10456-016-9502-0 1573-7209 Angiogenesis 26951478 http://hdl.handle.net/20.500.12105/17393 Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice.