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Cell free hemoglobin in the fetoplacental circulation : A novel cause of fetal growth restriction?

Brook, Adam ; Hoaksey, Annie ; Gurung, Rekha ; Yoong, Edward E.C. ; Sneyd, Rosanna ; Baynes, Georgia C. ; Bischof, Helen ; Jones, Sarah ; Higgins, Lucy E. and Jones, Carolyn , et al. (2018) In FASEB Journal 32(10). p.5436-5446
Abstract

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. FGRfetal 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... (More)

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. FGRfetal 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 sequesteredNOinacute andchronic exposuremodels (P<0.001), andfHbF-primed placental endothelial cellsdevelopedaproinflammatoryphenotype,demonstratedby activationofNF-κBpathway, 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.Thisunrecognizedmechanismfor fetal compromise offers a novel insight into FGRaswell as a potential explanation for associated poor fetal outcomes such as fetal demise and stillbirth.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Blood-flow resistance, Endothelium, Nitric oxide, Stillbirth, Vascular compromise
in
FASEB Journal
volume
32
issue
10
pages
11 pages
publisher
Wiley
external identifiers
  • pmid:29723064
  • scopus:85054071145
ISSN
0892-6638
DOI
10.1096/fj.201800264R
language
English
LU publication?
yes
id
d5b84d4f-8fab-4418-bce0-9e418b209b80
date added to LUP
2018-10-10 09:06:04
date last changed
2024-04-15 14:50:25
@article{d5b84d4f-8fab-4418-bce0-9e418b209b80,
  abstract     = {{<p>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. FGRfetal capillaries showed evidence of erythrocyte vascular packing and extravasation. Fetal cord blood fHbF levels were higher in FGR than in normal pregnancies (P &lt; 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&lt;0.05). fHbF sequesteredNOinacute andchronic exposuremodels (P&lt;0.001), andfHbF-primed placental endothelial cellsdevelopedaproinflammatoryphenotype,demonstratedby activationofNF-κBpathway, generation of IL-1α and TNF-α (both P &lt; 0.05), uncontrolled angiogenesis, and disruption of endothelial cell flow alignment. Elevated fHbF contributes to increased fetoplacental vascular resistance and impaired endothelial protection.Thisunrecognizedmechanismfor fetal compromise offers a novel insight into FGRaswell as a potential explanation for associated poor fetal outcomes such as fetal demise and stillbirth.</p>}},
  author       = {{Brook, Adam and Hoaksey, Annie and Gurung, Rekha and Yoong, Edward E.C. and Sneyd, Rosanna and Baynes, Georgia C. and Bischof, Helen and Jones, Sarah and Higgins, Lucy E. and Jones, Carolyn and Greenwood, Susan L. and Jones, Rebecca L. and Gram, Magnus and Lang, Ingrid and Desoye, Gernot and Myers, Jenny and Schneider, Henning and Hansson, Stefan R. and Crocker, Ian P. and Brownbill, Paul}},
  issn         = {{0892-6638}},
  keywords     = {{Blood-flow resistance; Endothelium; Nitric oxide; Stillbirth; Vascular compromise}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{5436--5446}},
  publisher    = {{Wiley}},
  series       = {{FASEB Journal}},
  title        = {{Cell free hemoglobin in the fetoplacental circulation : A novel cause of fetal growth restriction?}},
  url          = {{http://dx.doi.org/10.1096/fj.201800264R}},
  doi          = {{10.1096/fj.201800264R}},
  volume       = {{32}},
  year         = {{2018}},
}