Effects of Changes in Oxygen Tension on Vascular and Platelet Hydroxyacid Metabolites II. Hypoxia Increases 15-Hydroxyeicosatetraenoic Acid, a Proangiogenic Metabolite

Current strict O2 management may be precipitating more severe retinopathy of prematurity than would occur with a more lenient approach. Hypoxemia in an animal model has also been found to worsen retinal neovascularization. It has recently been shown that the hydroxyeicosatetraenoic acids can modulate angiogenesis. 15-Hydroxyeicosatetraenoic acid is proangiogenic, whereas 12-hydroxyeicosatetraenoic acid is an antiangiogenic metabolite. In vitro exposure of paired human neonatal vessels (n = 7) to hypoxia enhanced the production of total vascular hydroxyacids (232 ± 36 pmol/mg of protein [experimental group] v 168 ± 31 pmol [control group]; P < .01). The increase in vascular 15-hydroxyeicosatetraenoic acid under hypoxic conditions was even more significant (P < .001). However, platelet production of 12-hydroxyeicosatetraenoic acid was not significantly affected by hypoxia. These observations suggest a possible biochemical basis for the abnormal angiogenic process that occurs during the proliferation phase of the retinopathy of prematurity. The production of local hydroxyeicosatetraenoic acids in tissues manifesting abnormal neovascularization needs to be further evaluated.