title: Vitamin D improves endothelial dysfunction and restores myeloid angiogenic cell function via reduced CXCL-10 expression in systemic lupus erythematosus.
abstract: Patients with systemic lupus erythematosus (SLE) have accelerated cardiovascular disease and dysfunctional endothelial repair mechanisms. Myeloid angiogenic cells (MACs), derived from circulating monocytes, augment vascular repair by paracrine secretion of pro-angiogenic factors. We observed that SLE MACs are dysfunctional and secrete pro-inflammatory cytokines. We also found that the vitamin D receptor was transiently expressed during MAC differentiation and that in vitro, calcitriol increased differentiation of monocytes into MACs in both SLE and in a model using the prototypic SLE cytokine, interferon-alpha. The active form of vitamin D (calcitriol) restored the SLE MAC phenotype towards that of healthy subjects with reduced IL-6 secretion, and normalised surface marker expression. Calcitriol also augmented the angiogenic capacity of MACs via the down-regulation of CXCL-10. In SLE patients treated with cholecalciferol for 12 weeks, the improvement in endothelial function correlated with increase in serum 25(OH)D concentrations independently of disease activity. We also show that MACs were able to positively modulate eNOS expression in human endothelial cells in vitro, an effect further enhanced by calcitriol treatment of SLE MACs. The results demonstrate that vitamin D can positively modify endothelial repair mechanisms and thus endothelial function in a population with significant cardiovascular risk.
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.|Institute of Cardiovascular Science, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Reynolds
authors.affiliation: Rheumatology Department, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Sahena
authors.initials: S
authors.lastname: Haque
authors.affiliation: Institute of Cardiovascular Science, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.|Department of Musculoskeletal Biology, Faculty of Health &Life Sciences, University of Liverpool, Liverpool, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Williamson
authors.affiliation: Endocrine Sciences Research Group, Institute of Human Development, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Ray
authors.affiliation: Institute of Cardiovascular Science, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.|School of Healthcare Science, Manchester Metropolitan University, Manchester, UK.
authors.forename: M Yvonne
authors.initials: MY
authors.lastname: Alexander
authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Ian N
authors.initials: IN
authors.lastname: Bruce
mesh_terms: D000328:Adult; D002117:Calcitriol / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D007372:Interferons / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism* / Q000503:physiopathology*; D008875:Middle Aged; D008954:Models, Biological; D022423:Myeloid Cells / Q000187:drug effects / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010641:Phenotype; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D054357:Chemokine CXCL10; D014807:Vitamin D; D007372:Interferons; D052250:Nitric Oxide Synthase Type III; D002117:Calcitriol