Lupus-prone New Zealand Black/New Zealand White F1 mice display endothelial dysfunction and abnormal phenotype and function of endothelial progenitor cells

• Published in: Lupus Vol. 19; no. 3; pp. 288 - 299
• Main Authors: Thacker, SG, Duquaine, D., Park, J., Kaplan, MJ
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.03.2010; Sage Publications Ltd
• Subjects: Acetylcholine - pharmacology; Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Apoptosis; Atherosclerosis; Bone marrow; Disease; Disease Models, Animal; Down-Regulation; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Female; Genotype & phenotype; Interferon Type I - genetics; Interferon-alpha - metabolism; Internal medicine; Lupus; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - physiopathology; Medical schools; Mice; Mice, Inbred NZB; Muscle function; Nitroprusside - pharmacology; Phenotype; Potassium; Rheumatology; Smooth muscle; Stem Cells - metabolism; Vasodilator Agents - pharmacology; New Zealand; Ann Arbor Michigan; United States > US; endothelium; interferon-alpha; systemic lupus erythematosus; endothelial progenitor cells
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203309353773

Patients with systemic lupus erythematosus (SLE) have an impairment in phenotype and function of endothelial progenitor cells (EPCs) which is mediated by interferon α (IFN-α). 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 F1 (NZB/W), B6.MRL-Faslpr/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. Lupus (2010) 19, 288—299.