Expression of Placental FLT1 Transcript Variants Relates to Both Gestational Hypertensive Disease and Fetal Growth

The recent discovery of additional alternative spliced FLT1 transcripts encoding novel soluble (s)FLT1 protein isoforms complicates both the predictive value and functional implications of sFLT1 in preeclampsia. We investigated FLT1 expression levels and splicing patterns in placentas of normotensiv...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2011-07, Vol.58 (1), p.70-76
Main Authors: Jebbink, Jiska, Keijser, Remco, Veenboer, Geertruda, van der Post, Joris, Ris-Stalpers, Carrie, Afink, Gijs
Format: Article
Language:English
Subjects:
Adolescent
Adult
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Blood Pressure - physiology
Cardiology. Vascular system
Clinical manifestations. Epidemiology. Investigative techniques. Etiology
Female
Fetal Development - physiology
Gene Expression Regulation, Developmental
Gestational Age
Humans
Hypertension, Pregnancy-Induced - genetics
Hypertension, Pregnancy-Induced - metabolism
In Situ Hybridization
Infant, Newborn
Medical sciences
Placenta - metabolism
Polymerase Chain Reaction
Pregnancy
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Transcription, Genetic
Vascular Endothelial Growth Factor Receptor-1 - biosynthesis
Vascular Endothelial Growth Factor Receptor-1 - genetics
Young Adult
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Summary:The recent discovery of additional alternative spliced FLT1 transcripts encoding novel soluble (s)FLT1 protein isoforms complicates both the predictive value and functional implications of sFLT1 in preeclampsia. We investigated FLT1 expression levels and splicing patterns in placentas of normotensive and preeclamptic women, and established the tissue specificity of all FLT1 transcript variants. mRNA levels of sFLT1 splice variants were determined by real-time polymerase chain reaction in 21 normal human tissues and placental biopsies from 91 normotensive and 55 preeclamptic women. Cellular localization of placental FLT1 expression was established by RNA in situ hybridization. Of all tissues investigated, placenta has by far the highest FLT1 mRNA expression level, mainly localized in the syncytiotrophoblast layer. More than 80% of placental transcripts correspond to sFLT1_v2. Compared with normotensive placenta, preeclamptic placenta has ≈3-fold higher expression of all FLT1 transcript variants (P
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.110.164079