Plasma markers of angiogenesis in pregnancy induced hypertension.
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.
Nadar
Sunil K
SK
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Karalis
Ioannis
I
Al Yemeni
Eman
E
Blann
Andrew D
AD
Lip
Gregory Y H
GY
D000328:Adult; D042702:Angiopoietin-2 / Q000097:blood; D000803:Angiotensin I / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood*; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000097:blood*; D011225:Pre-Eclampsia / Q000097:blood; D011237:Predictive Value of Tests; D011247:Pregnancy; D042787:Receptor, TIE-2 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
D042702:Angiopoietin-2; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A; D000803:Angiotensin I; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1