Role of vitamin D in cell-cell interaction of fetal endothelial progenitor cells and umbilical cord endothelial cells in a preeclampsia-like model

• Published in: American Journal of Physiology: Cell Physiology Vol. 317; no. 2; p. C348
• Main Authors: Brodowski, L, Schröder-Heurich, B, Hubel, C A, Vu, T H, von Kaisenberg, C S, von Versen-Höynck, F
• Format: Journal Article
• Language: English
• Published: United States 01-08-2019
• Subjects: Adult; Calcitriol - pharmacology; Case-Control Studies; Cell Communication - drug effects; Cell Movement - drug effects; Cells, Cultured; Coculture Techniques; Culture Media, Conditioned - metabolism; Endothelial Progenitor Cells - drug effects; Endothelial Progenitor Cells - metabolism; Female; Fetal Stem Cells - drug effects; Fetal Stem Cells - metabolism; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Pre-Eclampsia - drug therapy; Pre-Eclampsia - metabolism; Pregnancy; Receptors, Calcitriol - agonists; Receptors, Calcitriol - genetics; Receptors, Calcitriol - metabolism; Signal Transduction; offspring health; fetal endothelial progenitor cells; preeclampsia; vitamin D
• ISSN: 1522-1563
• DOI: 10.1152/ajpcell.00109.2019

Maternal endothelial dysfunction is a cental feature of preeclampsia (PE), a hypertensive disorder of pregnancy. Factors in the maternal circulation are thought to contribute to this endothelial dysfunction. Although understudied, factors in the fetal circulation may influence fetal endothelial cell interactions with endothelial progenitor cells as critical steps in placental angiogenesis. We hypothesize that cell-cell interactions that are important for pregnancy health are impaired by fetal serum from PE pregnancies and that 1,25(OH)
-vitamin D
attenuates the negative effects of this serum on cell function. We tested the ability of fetal cord blood-derived endothelial progenitor cells [endothelial colony-forming cells (ECFCs)] to invade into established monolayers and capillary tubule-like structures of human fetal umbilical venous endothelial cells (HUVECs), while in the presence/absence of fetal cord serum from uncomplicated or PE pregnancies, and tested the ability of 1,25(OH)
-vitamin D
to modulate the serum-mediated effects. PE cord serum reduced the invasion of fetal ECFCs into HUVEC monolayers or tubule networks. Vitamin D attenuated these effects of PE fetal serum on endothelial functional properties. Immunocytochemical studies revealed involvement of VE-cadherin contacts in interactions between ECFCs and mature fetal endothelial cells. PE cord serum reduces the ability of fetal endothelial progenitor cells to incorporate into fetal endothelial cell networks. Physiologic concentrations of vitamin D reverse these PE serum-mediated effects. These data appear consistent with lines of evidence that vitamin D has antipreeclampsia effects.