Nitric oxide generation affects pro- and anti-angiogenic growth factor expression in primary human trophoblast.
Placenta
; 32(12): 926-31, 2011 Dec.
Article
en En
| MEDLINE
| ID: mdl-21963217
OBJECTIVES: Preeclampsia is associated with reduced trophoblast placenta growth factor (PGF) expression, elevated soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased bioactivity of nitric oxide (NO). Elevated sFlt-1 reduces bio-availability of PGF and vascular endothelial growth factor (VEGF) leading to maternal endothelial dysfunction. Although NO can regulate gene expression, its ability to regulate trophoblast expression of angiogenic growth factors is not known. STUDY DESIGN: Human primary term trophoblast and JEG-3 choriocarcinoma cells were cultured under 21%O(2) or 1%O(2) conditions in the presence or absence of NO donor (SNP) or inhibitor (L-NAME). Effects on PGF, VEGF and Flt-1 isoform mRNA expression were determined by quantitative real-time PCR. Changes in expression of soluble protein isoforms of FLT-1 was monitored by ELISA. RESULTS: Hypoxia decreased PGF mRNA but increased VEGF, sFlt-1 and Flt-1 mRNA expression in trophoblast. Generation of NO in trophoblast under 1%O(2) culture conditions significantly reversed sFlt-1 mRNA and protein expression, independent of mFlt-1. Conversely NO generation in hypoxic trophoblast increased VEGF and PGF mRNA expression. CONCLUSIONS: NO production in primary human trophoblast cultures had divergent effects on pro-angiogenic (PGF, VEGF) versus anti-angiogenic (sFlt-1) mRNA expression, resulting in an enhanced pro-angiogenic gene expression environment in vitro.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Gestacionales
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Trofoblastos
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NG-Nitroarginina Metil Éster
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Receptor 1 de Factores de Crecimiento Endotelial Vascular
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Hipoxia
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Óxido Nítrico
Límite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Placenta
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Países Bajos