title: 1α,25-dihydroxyvitamin D3 attenuates platelet activation and the expression of VCAM-1 and MT1-MMP in human endothelial cells.
abstract: OBJECTIVE
  Inflammatory conditions contribute to increased expression of various activity markers in platelets and endothelial cells, leading to atherosclerotic changes in the vascular wall. The objective of this study was to investigate possible protective effects of 1α,25-dihydroxyvitamin D3 in an endothelial cell model.
  
  
  METHODS
  After a 24-hour incubation with 1α,25-dihydroxyvitamin D3, human umbilical vein endothelial cells were stimulated with lipopolysaccharide (LPS) and incubated in direct contact with platelets. The expression of CD40L and CD62P in platelets, the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), the urokinase receptor uPAR and membrane type 1 matrix metalloproteinase (MT1-MMP) in endothelial cells and endothelial cell reactive oxygen species generation were measured by flow cytometry. Endothelial nitric oxide synthase was analyzed by Western blot.
  
  
  RESULTS
  The increased expression of VCAM-1 and MT1-MMP in endothelial cells by proinflammatory stimulation with LPS and by direct contact with activated platelets was significantly reduced through preincubation with 1α,25-dihydroxyvitamin D3. Platelets in direct contact with preincubated endothelial cells showed significantly reduced CD62P expression when compared to platelets incubated with untreated endothelial cells.
  
  
  CONCLUSIONS
  1α,25-Dihydroxyvitamin D3 attenuates platelet activation and the expression of VCAM-1 and MT1-MMP in human endothelial cells and could have early therapeutic relevance in atherosclerotic diseases.
authors.affiliation: 1st Department of Medicine, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Ksenija
authors.initials: K
authors.lastname: Stach
authors.forename: Anna-Isabelle
authors.initials: AI
authors.lastname: Kälsch
authors.forename: Xuan Duc
authors.initials: XD
authors.lastname: Nguyen
authors.forename: Elif
authors.initials: E
authors.lastname: Elmas
authors.forename: Stefan
authors.initials: S
authors.lastname: Kralev
authors.forename: Siegfried
authors.initials: S
authors.lastname: Lang
authors.forename: Christel
authors.initials: C
authors.lastname: Weiss
authors.forename: Martin
authors.initials: M
authors.lastname: Borggrefe
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kälsch
mesh_terms: D050197:Atherosclerosis / Q000517:prevention & control*; D015415:Biomarkers; D001792:Blood Platelets; D023201:CD40 Ligand; D002117:Calcitriol / Q000378:metabolism*; D042783:Endothelial Cells; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D019007:P-Selectin; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D023201:CD40 Ligand; D053511:Matrix Metalloproteinase 14; D002117:Calcitriol