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SHR Neuro Cancer Cardio Lipid Metab Microb

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
J CLIN ENDOCR METAB. 2021; 106(1): 26-41. Doi: 10.1210/clinem/dgaa403 [OPEN ACCESS]
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Co-authors Med Uni Graz: Desoye Gernot; Hoch Denise
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Abstract:: Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies. To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44. 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. 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. 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. 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. The FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes. © The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.
Find related publications in this database (Keywords): preeclampsia; angiogenesis; risk prediction; mesenchymal stem cell treatment; trophoblast cells; endothelial function