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

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journal contribution
posted on 2021-02-22, 17:28 authored by Naomi Todd, Ross McNally, Abdelrahim Alqudah, Djurdja Jerotic, Sonja Suvakov, Danilo Obradovic, Denise Hoch, Jose R Hombrebueno, Guillermo L Campos, Chris J Watson, Miroslava Gojnic-Dugalic, Tatjana P Simic, Anna Krasnodembskaya, 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 RobsonTracy Robson, Lana McClements

Context: Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.

Objective: To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.

Design and intervention: FKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling.

Settings and participants: Human samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, 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 signaling 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 of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>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 signaling, 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.


Invest Northern Ireland, Proof-of-Concept (POC 621)

Department for the Economy (DfE)–Global Challenge Research Fund (GCRF)

DfE PhD studentship, Northern Ireland.



The original article is available at

Published Citation

Todd N, McNally R, Alqudah A, Jerotic D, Suvakov S, Obradovic D, Hoch D, Hombrebueno JR, Campos GL, Watson CJ, Gojnic-Dugalic M, Simic TP, Krasnodembskaya A, Desoye G, Eastwood KA, Hunter AJ, Holmes VA, McCance DR, Young IS, Grieve DJ, Kenny LC, Garovic VD, Robson T, McClements L. Role of a novel angiogenesis FKBPL-CD44 pathway in preeclampsia risk stratification and mesenchymal stem cell treatment. Journal of Clinical Endocrinology & Metabolism. 2021;106(1):26-41.

Publication Date

3 July 2020

PubMed ID



  • School of Pharmacy and Biomolecular Sciences
  • Irish Centre for Vascular Biology

Research Area

  • Vascular Biology
  • Cancer
  • Immunity, Infection and Inflammation


Oxford University Press


  • Published Version (Version of Record)

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