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36 Type 1 interferon and endothelial progenitor cell function: development of an in vitro endothelial model of systemic lupus erythematosus
  1. J A Reynolds1,
  2. K Williamson2,
  3. T O'Neill1,
  4. D W Ray3,
  5. I N Bruce1,
  6. M Y Alexander2
  1. 1Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, UK
  2. 2Cardiovascular Research Group, University of Manchester, Manchester, UK
  3. 3Endocrine Sciences Research Group, University of Manchester, Manchester, UK

Abstract

Systemic Lupus Erythematosus (SLE) is associated with an increased risk of cardiovascular disease. Endothelial dysfunction in SLE correlates with circulating interferon (IFN) levels. Late-outgrowth endothelial progenitor cells (LO-EPCs) from lupus patients have impaired function which correlates with an increased expression of IFN-response genes (the IFN-signature). We aim to establish an in vitro model of SLE endothelial pathology, using IFN-α treatment of LO-EPC and human aortic endothelial cells (HAoEC), to develop novel preventative or reparative strategies for this disease. Late-outgrowth EPCs were isolated from human umbilical cord blood and characterised by immunocytochemistry and RT-PCR. HAoECs were cultured using standard protocols. Cell proliferation and tubule formation was analysed by MTT and Matrigel assays respectively. Connected tubes and branch points were counted 18 h after treatment with IFN2b or serum from SLE patients. Current studies involve establishing the interferon signature in endothelial cells, using a combination of microarray and Bioplex analysis. IFN-α-2b (10 ng/ml) results in reduced tubule formation by LO-EPCs but not HAoECs. SLE serum inhibits the proliferation of LO-EPCs but not HAoEcs in a dose-dependent manner. However, proliferation was not affected in either cell type by the addition of IFN-α-2b at concentrations up to 100 ng/ml at 24, 48 or 72 h. LO-EPCs are significantly affected in terms of their tube-forming capacity and proliferative response to IFN-α-2b and SLE serum respectively, while mature HAoECs lack this response to IFN2b. We conclude that LO-EPCs could be a target cell in SLE and offer a potential model for development of vasculoprotective therapies in these patients.

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