Soluble fms-like tyrosine kinase 1 is increased in preeclampsia but not in normotensive pregnancies with small-for-gestational-age neonates: relationship to circulating placental growth factor.
BACKGROUND
An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease.


OBJECTIVE
We asked whether, as with preeclampsia, sFlt-1 is increased and free PlGF is decreased in villous placenta and maternal serum of normotensive women with small-for-gestational-age (SGA) neonates.


METHODS
This was a case-control study using banked samples. Groups of women with SGA neonates (birth weight centile < 10th) and women with preeclampsia were matched to separate sets of normal pregnancy controls based on gestational age at blood sampling (serum) or gestational age at delivery (placenta).


RESULTS
sFlt-1 levels were higher in preeclamptics than controls (serum, P < 0.0001; placental protein, P = 0.03; placental mRNA, P = 0.007) but not increased in SGA pregnancies. PlGF was lower in both preeclampsia (serum, P < 0.0001; placental protein, P = 0.05) and SGA (serum, P = 0.0008; placental protein, P = 0.03) compared with their controls. PlGF in preeclampsia and SGA groups did not differ.


CONCLUSIONS
These data are consistent with a role for sFlt-1 in the maternal manifestations of preeclampsia. In contrast to preeclampsia, sFlt-1 does not appear to contribute substantially to decreased circulating free PlGF in SGA pregnancies in the absence of a maternal syndrome.
Shibata
Eiji
E
Magee-Womens Research Institute, University of Pittsburgh, 204 Craft Avenue, Pittsburgh, Pennsylvania 15213, USA.
Rajakumar
Augustine
A
Powers
Robert W
RW
Larkin
Robert W
RW
Gilmour
Carol
C
Bodnar
Lisa M
LM
Crombleholme
William R
WR
Ness
Roberta B
RB
Roberts
James M
JM
Hubel
Carl A
CA
D000328:Adult; D001794:Blood Pressure; D015153:Blotting, Western; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D010920:Placenta / Q000378:metabolism; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012995:Solubility
C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011506:Proteins; D012333:RNA, Messenger; D000072483:Placenta Growth Factor