ABSTRACT
Preeclampsia (PE) is the leading cause of maternal and fetal morbidity or mortality
but lacks reliable methods for early diagnosis. In a previous study, serum SERPINA5
levels were higher in women with PE before the clinical manifestation of the disease.
This study aimed to evaluate the efficacy of SERPINA5 in predicting PE and investigate
its role in trophoblast cell biology. A multicenter, 2-stage observational case-control
study was performed to develop and validate an early predictive PE model based on
SERPINA5, maternal characteristics, and inflammatory factors. To further understand
the relationship between SERPINA5 and PE, SERPINA5 was overexpressed or knocked down
in extravillous trophoblast cells (EVT) and a pregnant rat model. After development
and initial validation, a model that combined SERPINA5 and inflammatory factors had
a high predictive ability for PE before 20 weeks gestation with an AUC of 0.90 (95%
CI 0.83–0.96). It also demonstrated that SERPINA5 inhibited primary EVT cell invasion
by disrupting the urokinase-type plasminogen activator/urokinase-type plasminogen
activator receptor (uPA/uPAR) pathway, in turn, is involved in the development of
PE. In vivo experiments also proved that overexpression of SERPINA5 induced a PE-like
syndrome (hypertension and proteinuria) in pregnant rats. Therefore, serum SERPINA5
is a promising early biomarker of PE, suggesting that it may be involved in placental
development through its action on the uPA/uPAR system prior to the clinical manifestation
of PE.
Abbreviations:
AUC (area under the curve), CRP (C-reactive protein), EVT (extravillous trophoblast), FER (ferritin), HLA-G (histocompatibility antigen G), IL-6 (interleukin 6), ITGα5 (integrin alpha 5), ITGβ4 (integrin beta 4), ITGα6 (integrin alpha 6), ITGβ1 (integrin beta 1), LPS (lipopolysaccharide), MMP9 (matrix metalloproteinases 9), MMP2 (matrix metalloproteinases 2), PE (preeclampsia), SERPINA5 (serpin family A member 5), SERPINC1 (serum serpin family C member 1), uPA (urokinase-type plasminogen activator), uPAR (urokinase-type plasminogen activator receptor)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: June 14, 2022
Accepted:
June 10,
2022
Received in revised form:
May 24,
2022
Received:
March 1,
2022
Editor: Mr. M. FranklinPublication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
