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

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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 language	English
Journal	The Journal of Clinical Endocrinology & Metabolism
Early online date	03 Jul 2020
DOIs	https://doi.org/10.1210/clinem/dgaa403
Publication status	Published - 03 Jul 2020

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10.1210/clinem/dgaa403

Role of a novel angiogenesis FKBPL-CD44 pathway in preeclampsia risk stratification and mesenchymal stem cell treatment
© 2020 The Authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
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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 Thesis › Doctor 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

Todd, Naomi ; McNally, Ross ; Alqudah, Abdelrahim ; Jerotic, Djurdja ; Suvakov, Sonja ; Obradovic, Danilo ; Hoch, Denise ; Hombrebueno, Jose R ; Campos, Guillermo Lopez ; Watson, Chris J ; Gojnic-Dugalic, Miroslava ; Simic, Tatjana P ; Kransodembskaya, Anna ; Desoye, Gernot ; Eastwood, Kelly-Ann ; Hunter, Alyson J ; Holmes, Valerie A ; McCance, David R ; Young, Ian S ; Grieve, David J ; Kenny, Louise C ; Garovic, Vesna D ; Robson, Tracy ; McClements, Lana. / Role of a novel angiogenesis FKBPL-CD44 pathway in preeclampsia risk stratification and mesenchymal stem cell treatment. In: The Journal of Clinical Endocrinology & Metabolism. 2020.

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

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.",

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 Campos, {Guillermo Lopez} 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} Endocrine Society 2020.",

year = "2020",

month = jul,

day = "3",

doi = "10.1210/clinem/dgaa403",

language = "English",

journal = "The Journal of Clinical Endocrinology & Metabolism",

issn = "0021-972X",

publisher = "The Endocrine Society",

}

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, 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 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

Role of a novel angiogenesis FKBPL-CD44 pathway in preeclampsia risk stratification and mesenchymal stem cell treatment. / Todd, Naomi; McNally, Ross; Alqudah, Abdelrahim; Jerotic, Djurdja; Suvakov, Sonja; Obradovic, Danilo; Hoch, Denise; Hombrebueno, Jose R; Campos, Guillermo Lopez ; Watson, Chris J; Gojnic-Dugalic, Miroslava; Simic, Tatjana P; Kransodembskaya, Anna; Desoye, Gernot; Eastwood, Kelly-Ann; Hunter, Alyson J; Holmes, Valerie A; McCance, David R; Young, Ian S ; Grieve, David J; Kenny, Louise C; Garovic, Vesna D; Robson, Tracy; McClements, Lana.

In: The Journal of Clinical Endocrinology & Metabolism, 03.07.2020.

Research output: Contribution to journal › Article

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 - Campos, Guillermo Lopez

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

PY - 2020/7/3

Y1 - 2020/7/3

N2 - 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.

AB - 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.

U2 - 10.1210/clinem/dgaa403

DO - 10.1210/clinem/dgaa403

M3 - Article

C2 - 32617576

JO - The Journal of Clinical Endocrinology & Metabolism

JF - The Journal of Clinical Endocrinology & Metabolism

SN - 0021-972X

ER -