Fetal endothelium dysfunction is associated with circulating maternal levels of sE-selectin, sVCAM1, and sFlt-1 during pre-eclampsia

Abstract

Objectives. To evaluate the association between endothelial activation markers in the maternal circulation with nitric oxide (NO) synthesis in human umbilical endothelial cells.

Study design. This is a case-control study of normal and pre-eclamptic pregnancies. The levels of sE-selectin, soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble fms-like tyrosine kinase 1 (sFlt-1) were measured by enzyme-linked immunosorbent assay, and histamine-induced NO synthesis was detected by fluorometric examination of the human umbilical vein endothelial cells (HUVECs) isolated from normal and pathological pregnancies.

Results. Mothers with severe pre-eclamptic pregnancies have premature and smaller babies than mothers with normal pregnancies (P < 0.05); they also have high maternal plasma levels of sVCAM-1 (∼2-fold), sFlt-1 (∼2.5-fold), and lower (∼70%) histamine-stimulated NO synthesis in HUVECs. A positive relationship between systolic blood pressure (SBP) and plasma levels of sE-selectin, sVCAM-1, and sFlt-1 was demonstrated. Moreover, levels of sE-selectin, sVCAM-1, and sFlt-1 were negatively associated with newborn weight (NBW), gestational age at delivery, and NO synthesis. Women with high E-selectin (>63 ng/ml), VCAM-1 (>752 ng/ml), and sFlt-1 (>15204 pg/ml) showed high risk (∼2-fold) for preterm delivery and very preterm delivery, or fetal weight <1500 g (∼1.5-fold) compared with women with low levels.

Conclusions. High circulating levels of maternal endothelial dysfunction markers present in pre-eclampsia are associated with decreased NO synthesis in fetal endothelium.

Keywords:

• Endothelial dysfunctions
• pre-eclampsia pregnancy
• preterm labor
• newborn weight
• sE-selectin
• sVCAM-1
• sFlt-1
• gestational age
• nitric oxide

Acknowledgements

The research was supported by the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT Grants No. 11070035 and 1100684) Chile; Dirección de Investigación, Universidad de Concepción (DIUC Grants 205-072.031-1.0 and 207.084.009-1.0); and 0965091/RS from Dirección de Investigaciones, Universidad del Bío-Bío, Chile. We thank the midwives of Guillermo Grant Benavente Clinical Hospital and the labor ward of the Sanatorio Alemán Clinic, Concepción for the umbilical cord supply.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.