Role of a novel angiogenesis FKBPL-CD44 pathway in preeclampsia risk stratification and mesenchymal stem cell treatment

Research output: Contribution to journalArticlepeer-review

Authors

  • Naomi Todd
  • Ross McNally
  • Abdelrahim Alqudah
  • Djurdja Jerotic
  • Sonja Suvakov
  • Danilo Obradovic
  • Denise Hoch
  • Guillermo Lopez Campos
  • Chris J Watson
  • Miroslava Gojnic-Dugalic
  • Tatjana P Simic
  • Anna Kransodembskaya
  • Gernot Desoye
  • Kelly-Ann Eastwood
  • Alyson J Hunter
  • Valerie A Holmes
  • David R McCance
  • Ian S Young
  • David J Grieve
  • Louise C Kenny
  • Vesna D Garovic
  • Tracy Robson
  • Lana McClements

Colleges, School and Institutes

Abstract

Context
Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.
Objective
To investigate the diagnostic and therapeutic potential of the angiogenesis markers, FKBPL-CD44, in preeclampsia pathogenesis
Design and Intervention
FKBPL and CD44 plasma or placental concentration was determined in women pre- or post-diagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signalling.
Settings and Participants
Human samples pre-diagnosis (15 and 20 weeks’ gestation; n≥57), or post-diagnosis (n=18 for plasma; n=4 for placenta) of preeclampsia were used to determine FKBPL and CD44 concentration, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid.
Main outcome Measures
Preeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signalling in trophoblast and endothelial cells were assessed.
Results
The CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks’ gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.5-fold increased risk of preeclampsia (OR=2.5, 95% CI 1.12-5.41, p=0.02). In combination with high mean arterial blood pressure (MABP > 82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, p=0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signalling enhancing cell angiogenesis.
Conclusions
The FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.

Bibliographic note

© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Details

Original languageEnglish
Article numberdgaa403
JournalThe Journal of clinical endocrinology and metabolism
Volume2020
Publication statusPublished - 3 Jul 2020

Keywords

  • Pre-Eclampsia, Biomarkers, clinical assessment