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

FASEB J. 2019 Aug;33(8):9142-9153. doi: 10.1096/fj.201802750RR. Epub 2019 May 14.

Abstract

Endothelial colony-forming cells (ECFCs), a proliferative subpopulation of endothelial progenitor cells, are involved in angiogenesis and endothelial repair. In this study, we investigated endothelial barrier characteristics of ECFCs, whether vitamin D supports cell-cell adhesion and barrier integrity, and how it affects ECFC mobilization and actin dynamics. Although ECFC barrier was disrupted under inflammatory conditions, this effect was rescued by vitamin D treatment, leading to higher stability of an ECFC monolayer. Furthermore, vitamin D enhanced ECFC mobilization toward directional migration. In addition, immunocytochemistry, quantitative real-time PCR, and immunoblotting analysis showed that vitamin D increased endothelial interconnections through vascular endothelial cadherin (VE-cadherin) junctions and by impacting cell dynamics through cofilin and VE-cadherin phosphorylation. Our results suggest that vitamin D treatment efficiently counteracts inflammation in an ECFC monolayer, resulting in higher ECFC barrier integrity. This study provides evidence of a new beneficial effect of vitamin D for ECFC homeostasis.-Schröder-Heurich, B., von Hardenberg, S., Brodowski, L., Kipke, B., Meyer, N., Borns, K., von Kaisenberg, C. S., Brinkmann, H., Claus, P., von Versen-Höynck, F. Vitamin D improves endothelial barrier integrity and counteracts inflammatory effects on endothelial progenitor cells.

Keywords: TNF-α adhesion proteins; VE-cadherin; endothelial colony-forming cells; endothelial dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / drug effects
  • Antigens, CD / genetics
  • Antigens, CD / physiology
  • Cadherins / genetics
  • Cadherins / physiology
  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cells, Cultured
  • Coculture Techniques
  • Colony-Forming Units Assay
  • Endothelial Progenitor Cells / drug effects*
  • Endothelial Progenitor Cells / pathology
  • Endothelial Progenitor Cells / physiology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitamin D / pharmacology*
  • Vitamin D / physiology

Substances

  • Antigens, CD
  • Cadherins
  • Tumor Necrosis Factor-alpha
  • cadherin 5
  • Vitamin D