Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Fisicoquímica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1113AAD, Argentina.
Cells. 2021 Apr 3;10(4):800. doi: 10.3390/cells10040800.
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.
患有慢性高血压的女性所怀的妊娠，其并发子痫前期的风险增加，但涉及疾病进展的胎盘途径仍知之甚少。在这项研究中，我们使用易发生卒中的自发性高血压大鼠（SHRSP）模型来研究促进并发子痫前期的胎盘机制，重点关注细胞应激及其对半乳糖凝集素-聚糖通路的影响。我们的分析表明，SHRSP 胎盘的特征是细胞应激反应的持续激活，早在妊娠第 14 天（即疾病发作）就显示出脂质过氧化标志物（即硫代巴比妥酸反应物质（TBARS））和蛋白质硝化的显著增加水平，以及抗氧化酶表达缺陷。此外，凝集素分析表明，这种氧化还原失衡与胎盘糖码的明显改变有关，包括滋养层中核心 1 O-聚糖表达的明显减少和 SHRSP 胎盘中蜕膜中唾液酸化的增加。我们还观察到随着妊娠的进展，半乳糖凝集素 1、3 和 9 的表达发生显著变化，突出了半乳糖凝集素特征作为胎盘微环境挑战的动态解释者的重要作用。总的来说，我们的发现揭示了糖氧化还原平衡在并发子痫前期发病机制中的新作用，代表了针对妊娠高血压疾病干预的有希望的靶点。
