Role of a novel angiogenesis FKBPL-CD44 pathway in preeclampsia risk stratification and mesenchymal stem cell treatment.
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.
Invest Northern Ireland, Proof-of-Concept (POC 621)
Department for the Economy (DfE)–Global Challenge Research Fund (GCRF)
DfE PhD studentship, Northern Ireland.
CommentsThe original article is available at https://academic.oup.com/
Published CitationTodd 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 Date3 July 2020
- School of Pharmacy and Biomolecular Sciences
- Irish Centre for Vascular Biology
- Vascular Biology
- Immunity, Infection and Inflammation
PublisherOxford University Press
- Published Version (Version of Record)