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.
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机译：与更宽松的方法相比，目前严格的O2处理可能导致更严重的早产儿视网膜病变。还发现动物模型中的低氧血症会加剧视网膜新血管形成。最近显示，羟基二十碳四烯酸可调节血管生成。 15-羟基二十碳四烯酸是促血管生成的，而12-羟基二十碳四烯酸是抗血管生成的代谢产物。配对的人类新生儿血管（n = 7）在体外暴露于缺氧状态，可提高总血管羟酸的产生（232±36 pmol / mg蛋白质[实验组] v 168±31 pmol [对照组]; P <.01） 。在低氧条件下，血管15-羟基二十碳四烯酸的增加更为显着（P <.001）。然而，低氧对血小板产生的12-羟基二十碳四烯酸的影响不明显。这些观察结果提示了早产儿视网膜病变的增殖阶段发生的异常血管生成过程的可能的生化基础。在表现出异常新血管形成的组织中局部羟基二十碳四烯酸的产生需要进一步评估。
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