Plasma markers of angiogenesis in pregnancy induced hypertension

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

doi:10.1160/TH05-03-0167

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(05): 1071-1076
DOI: 10.1160/TH05-03-0167

Endothelium and Vascular Development

Schattauer GmbH

Plasma markers of angiogenesis in pregnancy induced hypertension

Sunil K. Nadar

¹Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK

,

Ioannis Karalis

¹Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK

,

Eman Al Yemeni

¹Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK

,

Andrew D. Blann

¹Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK

,

Gregory Y. H. Lip

¹Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK

› Author Affiliations

Abstract

Summary

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 ofVEGF; 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.

Keywords

Pregnancy induced hypertension - preeclampsia - vascular endothelial growth factor - angiopoietin-1 - angiopoietin-2 - angiogenesis

Full Text

References

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