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  Grieve; Louise C  Kenny; Vesna D Garovic; Tracy  Robson; Lana  McClements

doi:10.1210/clinem/dgaa403

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

Inflammation and Ageing

Research output: Contribution to journal › Article › peer-review

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 language	English
Article number	dgaa403
Pages (from-to)	26-41
Number of pages	16
Journal	The Journal of clinical endocrinology and metabolism
Volume	106
Issue number	1
Early online date	3 Jul 2020
DOIs	https://doi.org/10.1210/clinem/dgaa403
Publication status	Published - Jan 2021

Bibliographical 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.

Keywords

Pre-Eclampsia
Biomarkers
clinical assessment

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1210/clinem/dgaa403Licence: Creative Commons: Attribution (CC BY)

Cite this

Todd , N., McNally , R., Alqudah, A., Jerotic, D., Suvakov , S., Obradovic, D., Hoch, D., Hombrebueno, J. R., Lopez Campos, G., 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. (2021). Role of a novel angiogenesis FKBPL-CD44 pathway in preeclampsia risk stratification and mesenchymal stem cell treatment. The Journal of clinical endocrinology and metabolism, 106(1), 26-41. Article dgaa403. Advance online publication. https://doi.org/10.1210/clinem/dgaa403

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

abstract = "ContextPreeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.ObjectiveTo investigate the diagnostic and therapeutic potential of the angiogenesis markers, FKBPL-CD44, in preeclampsia pathogenesisDesign and InterventionFKBPL 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 ParticipantsHuman samples pre-diagnosis (15 and 20 weeks{\textquoteright} 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 MeasuresPreeclampsia 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.ResultsThe CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks{\textquoteright} 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.ConclusionsThe FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.",

keywords = "Pre-Eclampsia, Biomarkers, clinical assessment",

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

note = "{\textcopyright} 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.",

year = "2021",

month = jan,

doi = "10.1210/clinem/dgaa403",

language = "English",

volume = "106",

pages = "26--41",

journal = "The Journal of clinical endocrinology and metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

number = "1",

}

Todd , N, McNally , R, Alqudah, A, Jerotic, D, Suvakov , S, Obradovic, D, Hoch, D, Hombrebueno, JR, Lopez Campos, G, Watson, CJ, Gojnic-Dugalic, M, Simic, TP, Kransodembskaya, A, Desoye, G, Eastwood, K-A, Hunter, AJ, Holmes, VA, McCance , DR, Young, IS, Grieve, DJ, Kenny , LC, Garovic , VD, Robson, T & McClements, L 2021, 'Role of a novel angiogenesis FKBPL-CD44 pathway in preeclampsia risk stratification and mesenchymal stem cell treatment', The Journal of clinical endocrinology and metabolism, vol. 106, no. 1, dgaa403, pp. 26-41. https://doi.org/10.1210/clinem/dgaa403

TY - JOUR

T1 - Role of a novel angiogenesis FKBPL-CD44 pathway in preeclampsia risk stratification and mesenchymal stem cell treatment

AU - Todd , Naomi

AU - McNally , Ross

AU - Alqudah, Abdelrahim

AU - Jerotic, Djurdja

AU - Suvakov , Sonja

AU - Obradovic, Danilo

AU - Hoch, Denise

AU - Hombrebueno, Jose R

AU - Lopez Campos, Guillermo

AU - Watson, Chris J

AU - Gojnic-Dugalic, Miroslava

AU - Simic, Tatjana P

AU - Kransodembskaya, Anna

AU - Desoye, Gernot

AU - Eastwood, Kelly-Ann

AU - Hunter, Alyson J

AU - Holmes, Valerie A

AU - McCance , David R

AU - Young, Ian S

AU - Grieve, David J

AU - Kenny , Louise C

AU - Garovic , Vesna D

AU - Robson, Tracy

AU - McClements, Lana

N1 - © 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.

PY - 2021/1

Y1 - 2021/1

N2 - ContextPreeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.ObjectiveTo investigate the diagnostic and therapeutic potential of the angiogenesis markers, FKBPL-CD44, in preeclampsia pathogenesisDesign and InterventionFKBPL 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 ParticipantsHuman 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 MeasuresPreeclampsia 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.ResultsThe 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.ConclusionsThe FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.

AB - ContextPreeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.ObjectiveTo investigate the diagnostic and therapeutic potential of the angiogenesis markers, FKBPL-CD44, in preeclampsia pathogenesisDesign and InterventionFKBPL 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 ParticipantsHuman 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 MeasuresPreeclampsia 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.ResultsThe 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.ConclusionsThe FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.

KW - Pre-Eclampsia

KW - Biomarkers

KW - clinical assessment

U2 - 10.1210/clinem/dgaa403

DO - 10.1210/clinem/dgaa403

M3 - Article

C2 - 32617576

SN - 0021-972X

VL - 106

SP - 26

EP - 41

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 1

M1 - dgaa403

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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Cite this