The pathophysiological role and therapeutic relevance of vitamin D in preeclampsia

• Applicants: Professor Dr. Ralf Dechend; Professorin Dr. Frauke von Versen-Höynck
• Subject Area: Gynaecology and Obstetrics ; Reproductive Medicine, Urology
• Term: from 2014 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 263521300

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.

• DFG Programme: Research Grants