Abstract
Chorioamnionitis and funisitis are associated with neonatal morbidity and mortality. We hypothesized that chorioamnionitis may stress fetal endothelium, activate proinflammatory gene transcription. and affect angiogenic homeostasis in fetal capillaries. Placentas from preterm infants were stained for heat-shock protein 70, nuclear factor-κB, hypoxia-inducible factor-1α, and vascular endothelial growth factor (VEGF). VEGF receptors (VEGF-R) 1 and 2 as well as the receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE-2), which is involved in vascular remodeling, were quantified. Immunohistochemistry was analyzed by counting positive capillaries in placental terminal villi. Staining intensity was quantified by a three-step semiquantitative scale. The samples were divided into three matched groups according to histology: chorioamnionitis with funisitis (“funisitis”), chorioamnionitis without funisitis (“chorioamnionitis”), and control group with no inflammation. In tissues from the funisitis or chorioamnionitis group, heat-shock protein 70 expression was increased over the control group. More nuclear factor-κB–positive nuclei of endothelial cells in capillaries were counted in the funisitis and chorioamnionitis groups. Expression of VEGF and VEGF-R1 and -R2 were reduced in cases of funisitis or chorioamnionitis in comparison with controls. Hypoxia-inducible factor-1α expression tended to be slightly lower in the funisitis and chorioamnionitis groups but did not reach statistical significance. We speculate that cellular stress and changes in angiogenic homeostasis induced by proinflammatory activation of fetal endothelium in chorioamnionitis may not be limited to the placenta but may also involve other fetal organs.
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Abbreviations
- BPD:
-
bronchopulmonary dysplasia
- CI:
-
confidence interval
- HIF-1α:
-
hypoxia-inducible factor-1α
- HRP:
-
horseradish peroxidase
- HSP70:
-
heat-shock protein 70
- IL:
-
interleukin
- NF-κB:
-
nuclear factor-κB
- TIE-2:
-
tyrosine kinase with immunoglobulin and epidermal growth factor homology domains-2
- VEGF:
-
vascular endothelial growth factor
- VEGF-R:
-
vascular endothelial growth factor receptor
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This study was supported by a grant of the Interdisciplinary Center for Clinical Research (A-27) of the University of Würzburg, Germany.
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Kramer, B., Kaemmerer, U., Kapp, M. et al. Decreased Expression of Angiogenic Factors in Placentas with Chorioamnionitis after Preterm Birth. Pediatr Res 58, 607–612 (2005). https://doi.org/10.1203/01.PDR.0000175641.39056.7A
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DOI: https://doi.org/10.1203/01.PDR.0000175641.39056.7A
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