Erschienen in:
07.03.2016 | Original Paper
Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice
verfasst von:
Nieves García-Quintans, Cristina Sánchez-Ramos, Ignacio Prieto, Alberto Tierrez, Elvira Arza, Arantzazu Alfranca, Juan Miguel Redondo, María Monsalve
Erschienen in:
Angiogenesis
|
Ausgabe 2/2016
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Abstract
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.