Uteroplacental ischemia results in proteinuric hypertension and elevated sFLT-1.
Preeclampsia is a complication of pregnancy with significant morbidity and mortality for the mother and the fetus. Presumptions are made that placental hypoxia has a causative role in the clinical syndrome. Furthermore, soluble fms-like tyrosine kinase 1 (sFLT-1) has been shown to have a role in the maternal syndrome of preeclampsia. We investigated the relationship between uteroplacental ischemia (UPI), the maternal clinical syndrome of preeclampsia and sFLT-1 in non-human primates. The induction of UPI in a pregnant non-human primate resulted in the development of a clinical entity analogous to human preeclampsia. This was illustrated by the increase in blood pressure, development of proteinuria, and renal histological changes identical to human preeclampsia. A significant elevation in the placental and peripheral blood mononuclear cell sFLT-1 mRNA expression was noted, translating to a significant elevation in circulating sFLT-1. Thus, this sequence suggests that a pathogenic reduction in placental perfusion results in the development of the maternal syndrome of preeclampsia and an increase in circulating sFLT-1, which is derived both from placental and extra-placental sources.
Makris
A
A
Vascular Immunology Laboratory, Heart Research Institute and University of Sydney, NSW, Australia. makrisa@hri.org.au
Thornton
C
C
Thompson
J
J
Thomson
S
S
Martin
R
R
Ogle
R
R
Waugh
R
R
McKenzie
P
P
Kirwan
P
P
Hennessy
A
A
D000818:Animals; D005260:Female; D006973:Hypertension / Q000209:etiology*; D007511:Ischemia / Q000097:blood* / Q000150:complications*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000378:metabolism; D010215:Papio; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000209:etiology* / Q000473:pathology; D011247:Pregnancy; D011507:Proteinuria / Q000209:etiology*; D012333:RNA, Messenger / Q000378:metabolism; D014599:Uterus / Q000098:blood supply*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D040281:Vascular Endothelial Growth Factor Receptor-1