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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2907-2915. Prepublished online as a Blood First Edition Paper on July 16, 2007; DOI 10.1182/blood-2007-05-089086. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-089086v1 110/8/2907    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Denny, M. F. Articles by Kaplan, M. J. Search for Related Content PubMed PubMed Citation Articles by Denny, M. F. Articles by Kaplan, M. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Interferon- promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis Michael F. Denny1, Seth Thacker1,2, Hemal Mehta1, Emily C. Somers1, Todd Dodick1, Franck J. Barrat3, W. Joseph McCune1, and Mariana J. Kaplan1 1 Division of Rheumatology, Department of Internal Medicine and 2 Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor; 3 Dynavax Technologies, Berkeley, CA Individuals with systemic lupus erythematosus (SLE) have a striking increase in premature atherosclerosis of unclear etiology. Accelerated endothelial cell apoptosis occurs in SLE and correlates with endothelial dysfunction. Endothelial progenitor cells (EPCs) and myelomonocytic circulating angiogenic cells (CACs) are crucial in blood vessel repair after vascular damage, and decreased levels or abnormal function of EPCs/CACs are established atherosclerosis risk factors. We investigated if vascular repair is impaired in SLE. We report that SLE patients display abnormal phenotype and function of EPCs/CACs. These abnormalities are characterized by significant decreases in the number of circulating EPCs (310 ± 50 EPCs/mL of blood in SLE versus 639 ± 102 in controls) and significant impairments in the capacity of EPCs/CACs to differentiate into mature ECs and synthesize adequate levels of the proangiogenic molecules vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF). These abnormalities are triggered by interferon- (IFN-), which induces EPC and CAC apoptosis and skews myeloid cells toward nonangiogenic phenotypes. Lupus EPCs/CACs have increased IFN- expression and their supernatants promote higher induction of IFN-inducible genes. Importantly, neutralization of IFN pathways restores a normal EPC/CAC phenotype in lupus. SLE is characterized by an imbalance between endothelial cell damage and repair triggered by type I IFNs, which might promote accelerated atherosclerosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. E. Westerweel, R. H. W. M. Derksen, and M. C. Verhaar Comment on: Systemic lupus erythematosus patients exhibit functional deficiencies of endothelial progenitor cells Rheumatology, April 1, 2009; 48(4): 453 - 453. [Full Text] [PDF] J. Grisar, J. S. Smolen, and on behalf of the authors Comment on: Systemic lupus erythematosus patients exhibit functional deficiencies of endothelial progenitor cells: reply Rheumatology, April 1, 2009; 48(4): 453 - 454. [Full Text] [PDF] J H W Distler, Y Allanore, J Avouac, R Giacomelli, S Guiducci, F Moritz, A Akhmetshina, U A Walker, A Gabrielli, U Muller-Ladner, et al. EULAR Scleroderma Trials and Research group statement and recommendations on endothelial precursor cells Ann Rheum Dis, February 1, 2009; 68(2): 163 - 168. [Abstract] [Full Text] [PDF]

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