Plasma markers of angiogenesis in pregnancy induced hypertension

Sunil K. Nadar, Ioannis Karalis, Eman Al Yemeni, Andrew D. Blann, Gregory Y H Lip

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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.

Original languageEnglish
Pages (from-to)1071-1076
Number of pages6
JournalThrombosis and Haemostasis
Volume94
Issue number5
DOIs
Publication statusPublished - Nov 2005

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Keywords

  • Angiogenesis
  • Angiopoietin-1
  • Angiopoietin-2
  • Preeclampsia
  • Pregnancy induced hypertension
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Hematology

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