Cell free hemoglobin in the fetoplacental circulation: a novel cause of fetal growth restriction?
Cell free hemoglobin in the fetoplacental circulation: a novel cause of fetal growth restriction?
复制标题
DOI：
10.1096/fj.201800264r
复制
发表时间：
2018-10-01
期刊：
影响因子：
4.8
通讯作者：
Brownbill, Paul
中科院分区：
文献类型：
--
作者：
Brook, Adam;Hoaksey, Annie;Brownbill, Paul
游离血红蛋白损害成人心血管疾病患者的血管功能和血流。在这项研究中，我们调查的假设，即游离胎儿血红蛋白（fHbF）损害血管完整性和功能的胎儿胎盘循环，有助于增加血管阻力与胎儿生长受限（FGR）。招募了正常和FGR妊娠的妇女，并在产后新鲜收集她们的胎盘。FGR胎儿毛细血管显示红细胞血管填塞和外渗的证据。FGR的胎儿脐带血fHbF水平高于正常妊娠（P < 0.05），fHbF与血红素氧合酶-1相关的升高提示预期的分解代谢代偿失败，这发生在成人。在离体胎盘灌注过程中，病理生理fHbF浓度显著增加胎侧微循环阻力（P < 0.05）。在急性和慢性暴露模型中，fHbF隔离NO（P < 0.001），并且fHbF致敏的胎盘内皮细胞形成促炎表型，通过NF-B途径的激活、IL-1和TNF-α的产生（均P < 0.05）、不受控制的血管生成和内皮细胞流动排列的破坏来证明。升高的fHbF导致胎儿胎盘血管阻力增加和内皮保护受损。这种未被认识到的胎儿妥协机制提供了一种新的见解FGR以及相关的不良胎儿结局，如胎儿死亡和死产的潜在解释。Hoaksey，A.，古隆河Yoong，E. E. C.的方法，斯内德河，贝恩斯湾C.的方法，比肖夫，H.，琼斯，S.，希金斯湖E、琼斯角，澳-地Greenwood，S. L.，琼斯河，巴西-地L.，Gram，M.，朗岛Desoye，G.，Myers，J.，Schneider，H.，汉森，S。R.，克罗克岛P.，胎儿胎盘循环中的无细胞血红蛋白：胎儿生长受限的新原因？
Cell free hemoglobin impairs vascular function and blood flow in adult cardiovascular disease. In this study, we investigated the hypothesis that free fetal hemoglobin (fHbF) compromises vascular integrity and function in the fetoplacental circulation, contributing to the increased vascular resistance associated with fetal growth restriction (FGR). Women with normal and FGR pregnancies were recruited and their placentas collected freshly postpartum. FGR fetal capillaries showed evidence of erythrocyte vascular packing and extravasation. Fetal cord blood fHbF levels were higher in FGR than in normal pregnancies (P < 0.05) and the elevation of fHbF in relation to heme oxygenase-1 suggests a failure of expected catabolic compensation, which occurs in adults. During ex vivo placental perfusion, pathophysiological fHbF concentrations significantly increased fetal-side microcirculatory resistance (P < 0.05). fHbF sequestered NO in acute and chronic exposure models (P < 0.001), and fHbF-primed placental endothelial cells developed a proinflammatory phenotype, demonstrated by activation of NF-B pathway, generation of IL-1 and TNF- (both P < 0.05), uncontrolled angiogenesis, and disruption of endothelial cell flow alignment. Elevated fHbF contributes to increased fetoplacental vascular resistance and impaired endothelial protection. This unrecognized mechanism for fetal compromise offers a novel insight into FGR as well as a potential explanation for associated poor fetal outcomes such as fetal demise and stillbirth.Brook, A., Hoaksey, A., Gurung, R., Yoong, E. E. C., Sneyd, R., Baynes, G. C., Bischof, H., Jones, S., Higgins, L. E., Jones, C., Greenwood, S. L., Jones, R. L., Gram, M., Lang, I., Desoye, G., Myers, J., Schneider, H., Hansson, S. R., Crocker, I. P., Brownbill, P. Cell free hemoglobin in the fetoplacental circulation: a novel cause of fetal growth restriction?