Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble fms-like tyrosine kinase-1 expression.
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.
Gilbert
Jeffrey S
JS
Department of Physiology and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Babcock
Sara A
SA
Granger
Joey P
JP
D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000209:etiology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis / Q000502:physiology*
C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1