Plasma markers of angiogenesis in pregnancy induced hypertension

Thromb Haemost. 2005 Nov;94(5):1071-6. doi: 10.1160/TH05-03-0167.

Abstract

This study tests the hypothesis that abnormalities in plasma indices of angiogenesis, such as Vascular Endothelial Growth Factor (VEGF) and angiopoietins (Ang-1, Ang-2), as well as their soluble receptors Flt-1 (sFlt-1) and Tie 2 (sTie-2) respectively, are present in women with in pregnancy-induced hypertension (PIH). We also measured platelet levels of VEGF and Ang-1 (pVEGF and pAng-1 respectively). We studied 69 consecutive women with PIH (34 without proteinuria, and 35 with proteinuria, i.e. preeclampsia) who were compared to 64 consecutive women with normotensive pregnancies and 30 normotensive non-pregnant women, in a cross-sectional study. Using ELISA, we measured levels of plasma VEGF, Ang-1 & 2, Tie-2 and sFlt-1, and also the levels of angiogenic markers within the platelet [platelet VEGF (pVEGF) and platelet Ang-1 (pAng1)] by lysing a fixed number of platelets with 0.5% tween. Results show that levels of plasma VEGF, Ang-1, Ang2, sFlt-1 and Tie-2 were significantly different between the study groups. Post hoc analyses revealed plasma Ang-1 was highest in the preeclampsia group (p<0.001), whilst Ang-2 was highest in the normotensive pregnant group (p-=0.018). Plasma Tie-2 was highest in the PIH group. VEGF levels were significantly different between the preeclampsia group and the PIH group (p<0.05). Platelet VEGF levels were higher in the non-pregnant group than in the pregnant group, but there were no significant differences in the platelet levels of Ang-1 between the different groups. Ang-2, sFlt-1 and Tie-2 were undetectable in the platelet lysate in any of the patient groups or controls. Blood pressure was a major determinant of the different angiogenic factors studied. Abnormal indices of angiogenesis are evident in PIH and preeclampsia, with higher levels of sFlt-1 and lower levels of VEGF; in PIH, increased levels of Ang-1 and Tie-2, but reduced Ang-2, are evident compared to normal pregnancy. These abnormalities may have implications for the pathogenesis of PIH and preeclampsia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiopoietin-2 / blood
  • Angiotensin I / blood*
  • Biomarkers / blood
  • Female
  • Humans
  • Hypertension, Pregnancy-Induced / blood*
  • Multivariate Analysis
  • Neovascularization, Pathologic / blood*
  • Pre-Eclampsia / blood
  • Predictive Value of Tests
  • Pregnancy
  • Receptor, TIE-2 / blood
  • Vascular Endothelial Growth Factor A / blood*
  • Vascular Endothelial Growth Factor Receptor-1 / blood

Substances

  • Angiopoietin-2
  • Biomarkers
  • Vascular Endothelial Growth Factor A
  • Angiotensin I
  • Receptor, TIE-2
  • Vascular Endothelial Growth Factor Receptor-1