Abstract
Objective: Exposure to lower oxygen causes oxidative stress and promotes angiogenesis. Asphyctic neonates have shown higher cord-blood vascular endothelial growth factor (VEGF). We hypothesized that retina and choroid having a different circulatory regulation (choroid lacks vascular auto-regulation) would acutely stimulate angiogenesis in response to short and severe hypoxemia.
Methods: Retina/choroid were obtained from hypoxic (FiO2:8% x 30 min) newborn piglets resuscitated with 21% O2 and controls (ventilated with 21% O2) at 6h after birth. Vegfa mRNA expression was determined by real-time PCR. Protein level of hypoxia inducible factor-1alpha (HIF-1alpha), Vegf, phosphorylated p65 (S539), p65, and Gapdh (housekeeping gene) were studied by western blotting.
Results: Vegfa mRNA expression in retina and choroid significantly increased during hypoxia (p< 0.01 vs. control). At protein level, Hif-1α did not change significantly with hypoxia or re-oxygenation. Vegf protein did not increase in retina or choroid with hypoxia or re-oxygenation. P65 was significantly more phosphorylated in response to hypoxia (p< 0.05 vs. control), and restored to baseline after re-oxygenation just in retina. Total levels of p65 increased in choroid after 6h of resuscitation (p< 0.05 vs. control).
Conclusions:
-
i)
Short-term hypoxemia promotes p65 activation in retina and choroid.
-
ii)
Vegf-mRNA expression is not Hif-1α-dependent but secondary to p65-activation.
-
iii)
Angiogenic factors' synthesis has not been achieved due to time elapsed between hypoxemia and tissue extraction.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Solberg, R., Arduini, A., Escobar, J. et al. Asphyxia Activates P65 and Induces VEGF-A Gene Expression in Retina and Choroid from Newborn Piglets. Pediatr Res 70 (Suppl 5), 127 (2011). https://doi.org/10.1038/pr.2011.352
Issue Date:
DOI: https://doi.org/10.1038/pr.2011.352