Effects of normal and high circulating concentrations of activin A on vascular endothelial cell functions and vasoactive factor production.

Abstract

OBJECTIVES:

Activin A, a TGFβ family member, circulates in the maternal blood at increasing concentrations throughout gestation during a healthy pregnancy. The circulating concentration of activin A is further increased in pre-eclampsia (PE), a hypertensive disorder of pregnancy that is marked by systemic maternal vascular endothelial cell dysfunction. The effect of increasing activin A concentrations on the maternal vascular endothelium is unknown. The study aim was to investigate the effect of physiological and pathological activin A concentrations observed in normotensive and PE pregnancies respectively, on vascular endothelial cell function.

METHODS AND RESULTS:

Immunostaining demonstrated the presence of the activin A receptor, ACVR2A, in SGHEC-7 cells used to model the vascular endothelium. SGHEC-7 cells were treated with activin A concentrations representative of concentrations throughout gestation in normotensive (0-10ng/ml) and PE (50ng/ml) pregnancies. xCELLigence functional assays revealed that normotensive activin A concentrations increased SGHEC-7 proliferation and migration, which was inhibited by PE concentrations. Additionally, fluorescence based assays showed that PE concentrations increased endothelial permeability. None of the tested activin A concentrations affected cell apoptosis. PE concentrations also resulted in an imbalance of the vasoactive factors eNOS, PTGIS and EDN1, as determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays.

CONCLUSION:

Compared with normotensive activin A concentrations, the higher PE activin A concentrations resulted in abnormal endothelial functions, which may contribute to the systemic maternal vascular endothelial cell dysfunction observed in the disorder.

• Authors: Hannah E J Yong, Padma Murthi, May H Wong, Bill Kalionis, Judith E Cartwright, Shaun P Brennecke, Rosemary J Keogh
• Journal: Pregnancy hypertension (Pregnancy Hypertens) Vol. 5 Issue 4 Pg. 346-53 (Oct 2015) ISSN: 2210-7797 [Electronic] Netherlands
• PMID: 26597752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• activin A
• Activins
• Vascular Endothelial Growth Factor Receptor-1
• Activin Receptors, Type II
• activin receptor type II-A

Topics

• Activin Receptors, Type II (blood)
• Activins (blood)
• Adult
• Biomarkers (blood)
• Cell Culture Techniques
• Endothelium, Vascular (physiopathology)
• Female
• Humans
• Pre-Eclampsia (blood, diagnosis, physiopathology)
• Predictive Value of Tests
• Pregnancy
• Sensitivity and Specificity
• Vascular Endothelial Growth Factor Receptor-1 (blood)