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

Naomi Todd, Ross McNally, Abdelrahim Alqudah, Djurdja Jerotic, Sonja Suvakov, Danilo Obradovic, Denise Hoch, Jose R Hombrebueno, 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 GrieveLouise C Kenny, Vesna D Garovic, Tracy Robson, Lana McClements

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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.

Original languageEnglish
JournalThe Journal of Clinical Endocrinology & Metabolism
Early online date03 Jul 2020
DOIs
Publication statusPublished - 03 Jul 2020

Bibliographical note

© Endocrine Society 2020.

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  • Student Theses

    The role of FKBPL in diabetes and associated cardiovascular health

    Author: Alqudah, A., Dec 2019

    Supervisor: Grieve, D. (Supervisor), Lyons, T. (Supervisor) & McClements, L. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    Cite this

    Todd, N., McNally, R., Alqudah, A., Jerotic, D., Suvakov, S., Obradovic, D., Hoch, D., Hombrebueno, J. R., Campos, G. L., Watson, C. J., Gojnic-Dugalic, M., Simic, T. P., Kransodembskaya, A., Desoye, G., Eastwood, K-A., Hunter, A. J., Holmes, V. A., McCance, D. R., Young, I. S., ... McClements, L. (2020). Role of a novel angiogenesis FKBPL-CD44 pathway in preeclampsia risk stratification and mesenchymal stem cell treatment. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgaa403