Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble fms-like tyrosine kinase-1 expression

Jeffrey S. Gilbert, Sara A. Babcock, Joey P. Granger

Research output: Contribution to journalArticlepeer-review

225 Scopus citations

Abstract

The balance between proangiogenic and antiangiogenic factors, such as vascular endothelial growth factor, placental growth factor, and soluble fms-like tyrosine kinase-1 (sFlt-1), is altered in preeclampsia, and this dysregulation of angiogenic factors may be important in the pathogenesis of preeclampsia. Although sFlt-1 is elevated in preeclampsia, the mechanisms responsible for increasing this antiangiogenic factor remain unclear. We hypothesized that the hypertension produced by reduced uterine perfusion pressure (RUPP) is associated with increased sFlt-1 expression and decreased plasma vascular endothelial growth factor and placental growth factor concentrations in the pregnant rat. Arterial pressure was increased (130±3 versus 100±2 mm Hg; P<0.01) in the RUPP rats compared with the normal pregnant control rats. Plasma sFlt-1 concentration (660±270 versus 82±26 pg/mL; P<0.05) was increased, whereas plasma free placental growth factor (0.28±0.05 versus 1.7±0.5 pg/mL; P<0.01) and vascular endothelial growth factor (594±34 versus 830±33 pg/mL; P<0.01) concentrations were decreased in the RUPP rats compared with normal pregnant rats. Plasma sFlt-1:placental growth factor (37.2±7.8 versus 8.9±1.6; P<0.02) and sFlt-1:vascular endothelial growth factor (0.86±0.22 versus 0.28±0.06; P<0.05) ratios were increased in the RUPP rats compared with normal pregnant rats. Immunoreactive placental sFlt-1 was increased (1.1±0.1 versus 0.3±0.1; P<0.01) in RUPP rats contrasted with the normal pregnant rats. These findings support our hypothesis that RUPP increases the expression of sFlt-1 and alters the balance of angiogenic factors in the maternal circulation. These data also indicate that the RUPP model of pregnancy-induced hypertension may provide an invaluable model for mechanistic studies into the role of sFlt-1 in the pathogenesis preeclampsia.

Original languageEnglish (US)
Pages (from-to)1142-1147
Number of pages6
JournalHypertension
Volume50
Issue number6
DOIs
StatePublished - Dec 2007

Keywords

  • Angiogenic
  • Blood pressure
  • Gestation
  • Preeclampsia
  • VEGF

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