Galectin-glycan axis linking placental insufficiency and cardiovascular maladaptation (cardio-placenta axis): The role of vessel pathology

连接胎盘功能不全和心血管适应不良的半乳糖凝集素-聚糖轴（心脏-胎盘轴）：血管病理学的作用

• 批准号: 449662456
• 负责人: Professorin Dr. Sandra Maria Blois
• 金额: --
• 依托单位: Klinik für Geburtshilfe und Pränatalmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/449662456?language=en
• 关键词: Galectin; glycan; axis; linking; placental

Placental development involves a complex interaction between maternal cells and heavily glycosylated foetal trophoblasts. Failure of this process can cause preeclampsia (PE), one of the most common and deadly hypertensive complications of pregnancy. A history of PE increases cardiovascular disease (CVD) risk by two to four times for mother and child later in life. While the association between PE and chronic vascular disease is clear, the mechanism for this association is not known. Galectins (gal) are versatile translators of the glycocode, involved in regulating key reproductive processes (placentation, immune tolerance and angiogenesis) and cardiovascular health. Several studies have shown that an altered placental glycocode and placenta physiology associated with gal-1 dysregulation is linked to PE in humans and mice. These data suggest that an in-depth analysis of glycan/galectin signalling networks in pregnancy can define the molecular routes through which PE develops and contribute directly to cardiovascular disease pathogenesis. Therefore, the glycocode is a molecular master switch for a functional cardio-placental axis. This offers new opportunities for designing PE diagnosis and management strategies and improving long-term cardiovascular health in women and their offspring. This proposal seeks to crack the placental glycocode, unravelling the structural frameworks and recognition strategies of sugar-based interactions in placental tissue that relate to PE and CVD. Additionally, we aim to characterise the specific glycan/galectin signature that contributes to lasting endothelial dysfunction and an elevated risk of cardiovascular disease in women with a history of PE. We want to investigate if a pathological glycocode induces cardiac microvascular dysfunction and rarefaction, which leads to diastolic dysfunction with a pathological strain and strain rate. We hypothesize that the cardiovascular pathology after PE is caused by glycocode-induced cardiac small vessel disease. Since the glycocode is a concerted interplay of a multitude of factors, unravelling the cardio-placental axis will potentially contribute to identify strategies to prevent the progression of cardiovascular disease in women and offspring that experience PE.

胎盘发育涉及母体细胞和重度糖基化的胎儿滋养细胞之间复杂的相互作用。这一过程的失败可导致先兆子痫（PE），最常见和致命的妊娠高血压并发症之一。PE病史使母亲和孩子以后患心血管疾病（CVD）的风险增加2 - 4倍。虽然PE与慢性血管疾病之间的关联是明确的，但这种关联的机制尚不清楚。半乳糖凝集素（galectin, gal）是糖密码的多功能翻译器，参与调节关键的生殖过程（胎盘、免疫耐受和血管生成）和心血管健康。几项研究表明，与gal-1失调相关的胎盘糖密码改变和胎盘生理学与人类和小鼠的PE有关。这些数据表明，对妊娠期聚糖/凝集素信号网络的深入分析可以确定PE发展的分子途径，并直接促进心血管疾病的发病机制。因此，糖密码是功能心脏-胎盘轴的分子主开关。这为设计PE诊断和管理策略以及改善妇女及其后代的长期心血管健康提供了新的机会。本研究旨在破解胎盘糖密码，揭示与PE和CVD相关的胎盘组织中糖基相互作用的结构框架和识别策略。此外，我们的目标是描述特定的聚糖/凝集素特征，这有助于持久的内皮功能障碍和有PE病史的女性心血管疾病的风险增加。我们想要研究一个病理性糖密码是否会诱导心脏微血管功能障碍和稀疏，从而导致舒张功能障碍，并具有病理性应变和应变率。我们假设PE后的心血管病理是由糖糖诱导的心脏小血管病变引起的。由于糖密码是多种因素的协同相互作用，解开心脏-胎盘轴将潜在地有助于确定预防PE妇女及其后代心血管疾病进展的策略。