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

• Applicants: Professorin Dr. Sandra Maria Blois; Professor Dr. Ralf Dechend
• Subject Area: Gynaecology and Obstetrics ; Reproductive Medicine, Urology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 449662456

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.

• DFG Programme: Research Grants