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

Research output: Contribution to journalArticle

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.

Details

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

Keywords

  • Pre-Eclampsia, Biomarkers, clinical assessment