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 Krasnodembskaya, 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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)26-41
Number of pages16
JournalJournal of Clinical Endocrinology and Metabolism
Volume106
Issue number1
DOIs
StatePublished - Jan 1 2021

Keywords

  • angiogenesis
  • endothelial function
  • mesenchymal stem cell treatment
  • preeclampsia
  • risk prediction
  • trophoblast cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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