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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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posted on 22.02.2021, 17:28 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 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.

Funding

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

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

DfE PhD studentship, Northern Ireland.

History

Comments

The original article is available at https://academic.oup.com/

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

32617576

Department/Unit

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

Research Area

  • Vascular Biology
  • Cancer
  • Immunity, Infection and Inflammation

Publisher

Oxford University Press

Version

  • Published Version (Version of Record)