title: Brief Report: Vitamin D Deficiency Is Associated With Endothelial Dysfunction and Increases Type I Interferon Gene Expression in a Murine Model of Systemic Lupus Erythematosus.
abstract: Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD) and impaired endothelial repair. Although vitamin D deficiency is associated with increased CVD risk in the general population, a causal relationship has not been demonstrated. We aimed to determine whether vitamin D deficiency directly modulates endothelial dysfunction and immune responses in a murine model of SLE.
  
  
  
  Vitamin D deficiency was induced in lupus-prone MRL/lpr mice by dietary restriction for 6 weeks. Endothelium-dependent vasorelaxation was quantified using aortic ring myography, and endothelial repair mechanisms were assessed by evaluating the phenotype and function of bone marrow endothelial progenitor cells (EPCs) and with the use of an in vivo Matrigel plug model. Lupus disease activity was determined by evaluating expression of interferon-stimulated genes (ISGs) in splenic tissue, positivity for serum autoantibodies, and renal histology. To validate the findings, expression of ISGs was also measured in whole blood from vitamin D-deficient and vitamin D-sufficient patients with SLE.
  
  
  
  Vitamin D deficiency resulted in impaired endothelium-dependent vasorelaxation and decreases in neoangiogenesis without a change in the total number of EPCs. There were no differences in anti-double-stranded DNA titers, proteinuria, or glomerulonephritis (activity or chronicity) between vitamin D-deficient or sufficient mice. Vitamin D deficiency was associated with a trend toward increased ISG expression both in mice and in patients with SLE.
  
  
  
  These findings indicate that vitamin D deficiency is associated with hampered vascular repair and reduced endothelial function, and may modulate type I interferon responses.
authors.affiliation: NIH, Bethesda, Maryland, and Central Manchester University Hospital NHS Foundation Trust and Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Reynolds
authors.affiliation: Children's National Medical Center, Washington, DC, and NIH, Bethesda, Maryland.
authors.forename: Avi Z
authors.initials: AZ
authors.lastname: Rosenberg
authors.affiliation: NIH, Bethesda, Maryland.
authors.forename: Carolyne K
authors.initials: CK
authors.lastname: Smith
authors.affiliation: Central Manchester University Hospital NHS Foundation Trust, Manchester Academic Health Science Centre, and University of Manchester, Manchester, UK.
authors.forename: Jamie C
authors.initials: JC
authors.lastname: Sergeant
authors.affiliation: University of Manchester, Manchester, UK.
authors.forename: Gillian I
authors.initials: GI
authors.lastname: Rice
authors.affiliation: Central Manchester University Hospital NHS Foundation Trust and Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Briggs
authors.affiliation: Central Manchester University Hospital NHS Foundation Trust, Manchester Academic Health Science Centre, and University of Manchester, Manchester, UK.
authors.forename: Ian N
authors.initials: IN
authors.lastname: Bruce
authors.affiliation: NIH, Bethesda, Maryland.
authors.forename: Mariana J
authors.initials: MJ
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D001011:Aorta; D001323:Autoantibodies / Q000276:immunology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells; D004730:Endothelium, Vascular / Q000503:physiopathology*; D015870:Gene Expression; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D013058:Mass Spectrometry; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009213:Myography; D010281:Parathyroid Hormone / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D014664:Vasodilation; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000235:genetics / Q000503:physiopathology*
chemical_list: D001323:Autoantibodies; D007370:Interferon Type I; D010281:Parathyroid Hormone; D014807:Vitamin D; C104450:25-hydroxyvitamin D