Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, United Kingdom.
St. Mary's Hospital, Manchester University National Health Service (NHS) Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
FASEB J. 2018 Oct;32(10):5436-5446. doi: 10.1096/fj.201800264R. Epub 2018 May 3.
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-κB pathway, generation of IL-1α and TNF-α (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?
无细胞血红蛋白可损害成人心血管疾病中的血管功能和血流。在这项研究中，我们假设游离胎儿血红蛋白 (fHbF) 损害胎盘中的血管完整性和功能，导致与胎儿生长受限 (FGR) 相关的血管阻力增加。招募了正常妊娠和 FGR 妊娠的女性，并在产后立即采集胎盘。FGR 胎儿毛细血管显示出红细胞血管包装和渗出的证据。FGR 胎儿脐血 fHbF 水平高于正常妊娠（P <0.05），并且 fHbF 相对于血红素加氧酶-1 的升高表明预期的分解代谢补偿失败，这在成人中发生。在胎盘离体灌注期间，病理生理 fHbF 浓度显着增加胎儿侧微血管阻力（P <0.05）。fHbF 在急性和慢性暴露模型中隔离 NO（P <0.001），并且 fHbF 引发的胎盘内皮细胞表现出促炎表型，这通过 NF-κB 途径的激活、IL-1α 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排列的破坏来证明。升高的 fHbF 导致胎盘中血管阻力增加和内皮保护受损。这种胎儿损害的未被认识的机制为 FGR 提供了新的见解，并为相关的不良胎儿结局（例如胎儿死亡和死产）提供了潜在的解释。-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. 胎盘中的无细胞血红蛋白：胎儿生长受限的新原因？
