Uteroplacental ischemia results in proteinuric hypertension and elevated sFLT-1

• Published in: Kidney international Vol. 71; no. 10; pp. 977 - 984
• Main Authors: Makris, A., Thornton, C., Thompson, J., Thomson, S., Martin, R., Ogle, R., Waugh, R., McKenzie, P., Kirwan, P., Hennessy, A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2007; Elsevier Limited
• Subjects: Animals; Female; hypertension; Hypertension - etiology; Ischemia - blood; Ischemia - complications; Kidney - metabolism; Kidney - pathology; Monocytes - metabolism; Papio; Placenta - blood supply; Placenta - metabolism; Pre-Eclampsia - etiology; Pre-Eclampsia - pathology; preeclampsia; Pregnancy; proteinuria; Proteinuria - etiology; RNA, Messenger - metabolism; sFLT-1; Uterus - blood supply; Vascular Endothelial Growth Factor Receptor-1 - blood; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular Endothelial Growth Factor Receptor-1 - metabolism; preeclampsia; sFLT-1; hypertension; proteinuria
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/sj.ki.5002175

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.