Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

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, K-A; 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.

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, K-A Hunter, AJ Holmes, VA McCance, DR Young, IS Grieve, DJ Kenny, LC Garovic, VD Robson, T McClements, L

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Publisher:: The Endocrine Society
Publication Type:: Journal Article
Citation:: The Journal of clinical endocrinology and metabolism, 2021, 106, (1), pp. 26-41
Issue Date:: 2021-01

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Field	Value	Language
dc.contributor.author	Todd, N
dc.contributor.author	McNally, R
dc.contributor.author	Alqudah, A
dc.contributor.author	Jerotic, D
dc.contributor.author	Suvakov, S
dc.contributor.author	Obradovic, D
dc.contributor.author	Hoch, D
dc.contributor.author	Hombrebueno, JR
dc.contributor.author	Campos, GL
dc.contributor.author	Watson, CJ
dc.contributor.author	Gojnic-Dugalic, M
dc.contributor.author	Simic, TP
dc.contributor.author	Krasnodembskaya, A
dc.contributor.author	Desoye, G
dc.contributor.author	Eastwood, K-A
dc.contributor.author	Hunter, AJ
dc.contributor.author	Holmes, VA
dc.contributor.author	McCance, DR
dc.contributor.author	Young, IS
dc.contributor.author	Grieve, DJ
dc.contributor.author	Kenny, LC
dc.contributor.author	Garovic, VD
dc.contributor.author	Robson, T
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014
dc.date.accessioned	2021-02-04T02:58:11Z
dc.date.available	2021-02-04T02:58:11Z
dc.date.issued	2021-01
dc.identifier.citation	The Journal of clinical endocrinology and metabolism, 2021, 106, (1), pp. 26-41
dc.identifier.issn	0021-972X
dc.identifier.issn	1945-7197
dc.identifier.uri	http://hdl.handle.net/10453/145812
dc.description.abstract	<h4>Context</h4>Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.<h4>Objective</h4>To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.<h4>Design and intervention</h4>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.<h4>Settings and participants</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>The FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes.
dc.format	Print
dc.language	eng
dc.publisher	The Endocrine Society
dc.relation.ispartof	The Journal of clinical endocrinology and metabolism
dc.relation.isbasedon	10.1210/clinem/dgaa403
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine
dc.subject.classification	Endocrinology & Metabolism
dc.title	Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.
dc.type	Journal Article
utslib.citation.volume	106
utslib.location.activity	United States
utslib.for	1103 Clinical Sciences
utslib.for	1114 Paediatrics and Reproductive Medicine
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
dc.date.updated	2021-02-04T02:58:01Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	106
utslib.citation.issue	1

Abstract:

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/145812