The pathophysiological role and therapeutic relevance of vitamin D in preeclampsia

维生素 D 在先兆子痫中的病理生理作用和治疗相关性

• 批准号: 263521300
• 负责人: Professor Dr. Ralf Dechend
• 金额: --
• 依托单位: Klinik für Frauenheilkunde und Geburtshilfe
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/263521300?language=en
• 关键词: pathophysiological; role; therapeutic; relevance; vitamin

The pregnancy syndrome preeclampsia that is characterized by new onset hypertension and proteinuria in the second half of pregnancy represents one of the major reasons for fetal and maternal morbidity and mortality in Europe and is associated with an increased risk for cardiovascular disease later in life for mother and child. Effective preventive or predictive strategies dont exist to date so that currently the only effective treatment is the delivery of the baby. Low vitamin D concentrations are associated with a 5-fold risk for the development of preeclampsia. The mechanisms that connect vitamin D deficiency and preeclampsia are not understood. Our previous experiments show a promoting effect of vitamin D on trophoblast and endothelial cell function and their homeostasis. We found, that vitamin D facilitates proliferation, migration and tubulus formation of endothelial progenitor cells by activating VEGF secretion. Moreover, vitamin D neutralized the negative effects of placenta derived pathogenic factors on endothelial progenitor cell function. We hypothesize that vitamin D plays an important role for feto-placental and maternal-endothelial inflammatory and angiogenic responses during pregnancy and that vitamin D deficiency is one pathophysiologic reason for the development of preeclampsia. With this proposal we want to prove that low maternal concentrations contribute to a dysregulation of placental and endothelial processes. Vitamin D sufficiency would improve placental and endothelial reactions and eventually pregnancy outcome. The aim of our future research is to expand our work and to examine, if and how vitamin D affects the two main pathophysiologic aspects of preeclampsia. In the proposed project we plan to use in vitro and in vivo models to (1) investigate the effect of vitamin D on placental angiogenesis and (2) on maternal endothelial cell homeostasis and repair capacity. Further understanding of the role of vitamin D in the regulation of these mechanisms is a necessary and important step to further evaluate the potential of vitamin D as preventive/therapeutic agent in preeclampsia.

妊娠综合征先兆子痫的特征是妊娠后半期新发高血压和蛋白尿，是欧洲胎儿和孕产妇发病率和死亡率的主要原因之一，与母亲和儿童日后患心血管疾病的风险增加有关。有效的预防或预测策略迄今为止还不存在，因此目前唯一有效的治疗方法是分娩。低维生素D浓度与先兆子痫发展的5倍风险相关。维生素D缺乏症和先兆子痫的联系机制尚不清楚。我们以前的实验表明，维生素D对滋养层和内皮细胞功能及其稳态的促进作用。我们发现，维生素D通过激活VEGF分泌促进内皮祖细胞的增殖、迁移和小管形成。此外，维生素D中和了胎盘源性致病因子对内皮祖细胞功能的负面影响。我们假设维生素D在妊娠期间胎儿-胎盘和母体-内皮炎症和血管生成反应中起重要作用，维生素D缺乏是先兆子痫发生的病理生理原因之一。通过这一提议，我们想证明母体低浓度有助于胎盘和内皮过程的失调。维生素D充足可改善胎盘和内皮反应，最终改善妊娠结局。我们未来研究的目的是扩大我们的工作，并检查维生素D是否以及如何影响先兆子痫的两个主要病理生理学方面。在拟议的项目中，我们计划使用体外和体内模型来（1）研究维生素D对胎盘血管生成的影响和（2）对母体内皮细胞稳态和修复能力的影响。进一步了解维生素D在调节这些机制中的作用是进一步评估维生素D作为先兆子痫预防/治疗剂的潜力的必要和重要的一步。

项目成果

Vitamin D improves endothelial barrier integrity and counteracts inflammatory effects on endothelial progenitor cells

维生素 D 改善内皮屏障完整性并抵消内皮祖细胞的炎症影响

• DOI: 10.1096/fj.201802750rr
• 发表时间: 2019
• 期刊: The FASEB Journal
• 作者: Schröder-Heurich B;von Hardenberg S;Brodowski L;Kipke B;Meyer N;Borns K;von Kaisenberg CS;Brinkmann H;Claus P;von Versen-Höynck F
• 通讯作者: von Versen-Höynck F