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Placental glycoredox dysregulation associated with disease progression in an animal model of superimposed preeclampsia

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Item Type:Article
Title:Placental glycoredox dysregulation associated with disease progression in an animal model of superimposed preeclampsia
Creators Name:Blois, S.M. and Prince, P.D. and Borowski, S. and Galleano, M. and Barrientos, G.
Abstract:Pregnancies carried by women with chronic hypertension are at increased risk of superimposed preeclampsia, but the placental pathways involved in disease progression remain poorly understood. In this study, we used the stroke-prone spontaneously hypertensive rat (SHRSP) model to investigate the placental mechanisms promoting superimposed preeclampsia, with focus on cellular stress and its influence on galectin–glycan circuits. Our analysis revealed that SHRSP placentas are characterized by a sustained activation of the cellular stress response, displaying significantly increased levels of markers of lipid peroxidation (i.e., thiobarbituric acid reactive substances (TBARS)) and protein nitration and defective antioxidant enzyme expression as early as gestation day 14 (which marks disease onset). Further, lectin profiling showed that such redox imbalance was associated with marked alterations of the placental glycocode, including a prominent decrease of core 1 O-glycan expression in trophoblasts and increased decidual levels of sialylation in SHRSP placentas. We also observed significant changes in the expression of galectins 1, 3 and 9 with pregnancy progression, highlighting the important role of the galectin signature as dynamic interpreters of placental microenvironmental challenges. Collectively, our findings uncover a new role for the glycoredox balance in the pathogenesis of superimposed preeclampsia representing a promising target for interventions in hypertensive disorders of pregnancy.
Keywords:Chronic Hypertension, Placenta, Preeclampsia, Oxidative Stress, Glycosylation, Animals, Rats
Page Range:800
Date:April 2021
Official Publication:https://doi.org/10.3390/cells10040800

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