title: Lupus-prone New Zealand Black/New Zealand White F1 mice display endothelial dysfunction and abnormal phenotype and function of endothelial progenitor cells.
abstract: Patients with systemic lupus erythematosus (SLE) have an impairment in phenotype and function of endothelial progenitor cells (EPCs) which is mediated by interferon alpha (IFN-alpha). We assessed whether murine lupus models also exhibit vasculogenesis abnormalities and their potential association with endothelial dysfunction. Phenotype and function of EPCs and type I IFN gene signatures in EPC compartments were assessed in female New Zealand Black/New Zealand White F(1) (NZB/W), B6.MRL-Fas(lpr)/J (B6/lpr) and control mice. Thoracic aorta endothelial and smooth muscle function were measured in response to acetylcholine or sodium nitropruside, respectively. NZB/W mice displayed reduced numbers, increased apoptosis and impaired function of EPCs. These abnormalities correlated with significant decreases in endothelium-dependent vasomotor responses and with increased type I IFN signatures in EPC compartments. In contrast, B6/lpr mice showed improvement in endothelium-dependent and endothelial-independent responses, no abnormalities in EPC phenotype or function and downregulation of type I IFN signatures in EPC compartments. These results indicate that NZB/W mice represent a good model to study the mechanisms leading to endothelial dysfunction and abnormal vasculogenesis in lupus. These results further support the hypothesis that type I IFNs may play an important role in premature vascular damage and, potentially, atherosclerosis development in SLE.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-5680, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Thacker
authors.forename: D
authors.initials: D
authors.lastname: Duquaine
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.forename: M J
authors.initials: MJ
authors.lastname: Kaplan
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis; D004195:Disease Models, Animal; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007370:Interferon Type I / Q000235:genetics*; D016898:Interferon-alpha / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008814:Mice, Inbred NZB; D009599:Nitroprusside / Q000494:pharmacology; D010641:Phenotype; D013234:Stem Cells / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D007370:Interferon Type I; D016898:Interferon-alpha; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine