A longitudinal study of circulating angiogenic and antiangiogenic factors and AT1-AA levels in preeclampsia

Hypertens Res. 2014 Aug;37(8):753-8. doi: 10.1038/hr.2014.71. Epub 2014 Apr 10.

Abstract

Our earlier studies of preeclampsia (PE) at delivery have demonstrated the alteration of one carbon cycle, reduced placental omega 3 fatty acids, altered circulating levels of angiogenic factors and differential placental gene-specific methylation patterns of angiogenic factors. This study was undertaken to examine changes in the levels of angiogenic factors and angiotensin II type 1 receptor autoantibodies (AT1-AAs) throughout gestation, from early pregnancy until delivery, in women with PE and to examine their association with cord angiogenic factors, blood pressure and infant weight. A total of 81 pregnant women (46 normotensive and 35 with PE) were followed at three different time points during pregnancy: 16-20 weeks (T1), 26-30 weeks (T2) and at the time of delivery (T3). The plasma levels of angiogenic factors and AT1-AAs were determined in the maternal and cord plasma by commercial enzyme-linked immunosorbent assay kits. Maternal plasma levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were lower (P<0.05 for both), whereas soluble fms-like tyrosine kinase-1 (sFlt-1; P<0.05) and the sFlt-1/PlGF ratio (P<0.01) were higher in early pregnancy in the PE group. Maternal plasma AT1-AA levels were higher (P<0.05) at T2 in women with PE. Cord plasma VEGF and soluble kinase insert domain receptor (sKDR) levels were lower (P<0.01 and P<0.05, respectively), whereas AT1-AA levels were higher (P<0.05) in the PE group. Maternal plasma VEGF levels in early pregnancy were positively associated with systolic blood pressure, whereas the sFlt-1/PlGF ratio at T2 was negatively associated with infant weight in the PE group. Low levels of proangiogenic factors (VEGF and PlGF) and high levels of AT1-AAs and antiangiogenic factors (sFlt-1 and sFlt-1/PlGF ratio) are present in the maternal circulation during early gestation in women with PE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiogenic Proteins / metabolism*
  • Autoantibodies / analysis*
  • Birth Weight
  • Blood Pressure / physiology
  • Female
  • Fetal Development / genetics
  • Fetal Development / physiology
  • Humans
  • Infant, Newborn
  • Longitudinal Studies
  • Placenta Growth Factor
  • Pre-Eclampsia / blood*
  • Pregnancy
  • Pregnancy Proteins / blood
  • Receptor, Angiotensin, Type 1 / immunology*
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-1 / blood
  • Vascular Endothelial Growth Factor Receptor-2 / blood

Substances

  • Angiogenic Proteins
  • Autoantibodies
  • PGF protein, human
  • Pregnancy Proteins
  • Receptor, Angiotensin, Type 1
  • Vascular Endothelial Growth Factor A
  • Placenta Growth Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2