Soluble fms-like tyrosine kinase-1 and soluble endoglin in HIV-associated preeclampsia.

Abstract

OBJECTIVE:

Preeclampsia is characterized by endothelial dysfunction combined with increased concentrations of sFlt1, which antagonizes the biological effects of VEGF and PlGF, and of sEng, which antagonizes TGFβ1. This angiogenic imbalance may have a role in its etiology. This study evaluated the expression of VEGF, PlGF, sFlt1 and sEng amongst third trimester pregnancies in women with HIV-associated pre-eclampsia.

METHOD:

Serum and placental tissue were obtained from 76 pregnancies in women who were normotensive and HIV negative (N-) or positive (N+), and in women who were pre-eclamptic and HIV negative (P-) or positive (P+). The serum and placental samples were quantitatively evaluated using ELISAs and RT-PCR respectively.

RESULTS:

Placental sFlt1 expression differed significantly between the N- and P- groups (p=0.001). Similarly, sEng expression differed between the N- and P- groups (p=0.001). No significant effect was shown between HIV status and pregnancy. Serum sFlt1 (p=0.02) and sEng (p=0.001) were up-regulated in the P- compared to the N- groups. Similarly, no significant effect was shown between HIV status and pregnancy. Both VEGF and PlGF did not differ significantly between groups. Notably, sEng expression was elevated in both placenta and serum, whilst placental sFlt1 differed from serum. A weak but significant correlation between serum and placental concentration for sFlt1, sEng and PlGF (r=0.26, p=0.031; r=0.42, p<0.001 and r=-0.3, p=0.014) was observed.

CONCLUSIONS:

This novel study demonstrates an up-regulation of serum sFlt1 and sEng in preeclamptic compared to normotensive groups irrespective of the HIV status of the pregnancy. This implicates a contributory role of sFlt1 and sEng in preeclampsia development. The serum reduction of sFlt1 and sEng within the HIV positive compared to HIV negative cohorts may imply a neutralization of the immune hyperreactivity of preeclampsia.

• Authors: Nalini Govender, Thajasvarie Naicker, Augustine Rajakumar, Jagidesa Moodley
• Journal: European journal of obstetrics, gynecology, and reproductive biology (Eur J Obstet Gynecol Reprod Biol) Vol. 170 Issue 1 Pg. 100-5 (Sep 2013) ISSN: 1872-7654 [Electronic] Ireland
• PMID: 23806447 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antigens, CD
• ENG protein, human
• Endoglin
• PGF protein, human
• Pregnancy Proteins
• RNA, Messenger
• Receptors, Cell Surface
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Placenta Growth Factor
• FLT1 protein, human
• Vascular Endothelial Growth Factor Receptor-1

Topics

• Adult
• Antigens, CD (blood)
• Case-Control Studies
• Endoglin
• Female
• HIV Infections (blood, complications)
• Humans
• Placenta (metabolism)
• Placenta Growth Factor
• Pre-Eclampsia (blood, etiology)
• Pregnancy
• Pregnancy Complications, Infectious (blood)
• Pregnancy Proteins (blood)
• RNA, Messenger (metabolism)
• Real-Time Polymerase Chain Reaction
• Receptors, Cell Surface (blood)
• Vascular Endothelial Growth Factor A (blood)
• Vascular Endothelial Growth Factor Receptor-1 (blood)
• Young Adult