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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3872-3879. Prepublished online as a Blood First Edition Paper on December 21, 2007; DOI 10.1182/blood-2007-06-097188. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-06-097188v1 111/7/3872    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 Chang Milbauer, L. Articles by Hebbel, R. P. Search for Related Content PubMed PubMed Citation Articles by Chang Milbauer, L. Articles by Hebbel, R. P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Red Cells Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Genetic endothelial systems biology of sickle stroke risk Liming Chang Milbauer1, Peng Wei1,2, Judy Enenstein1, Aixiang Jiang1,2, Cheryl A. Hillery3, J. Paul Scott3, Stephen C. Nelson4, Vidya Bodempudi1, James N. Topper5, Ruey-Bing Yang5, Betsy Hirsch6, Wei Pan2, and Robert P. Hebbel1 1 Vascular Biology Center and Division of Hematology-Oncology-Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis; 2 Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis; 3 Blood Research Institute, Children's Research Institute, Medical College of Wisconsin, Milwaukee; 4 Minneapolis Children's' Hospital and Department of Pediatrics, University of Minnesota Medical School, Minneapolis; 5 Millennium Pharmaceuticals, San Francisco CA; and 6 Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis Genetic differences in endothelial biology could underlie development of phenotypic heterogeneity among persons afflicted with vascular diseases. We obtained blood outgrowth endothelial cells from 20 subjects with sickle cell anemia (age, 4-19 years) shown to be either at-risk (n = 11) or not-at-risk (n = 9) for ischemic stroke because of, respectively, having or not having occlusive disease at the circle of Willis. Gene expression profiling identified no significant single gene differences between the 2 groups, as expected. However, analysis of Biological Systems Scores, using gene sets that were predetermined to survey each of 9 biologic systems, showed that only changes in inflammation signaling are characteristic of the at-risk subjects, as supported by multiple statistical approaches. Correspondingly, subsequent biologic testing showed significantly exaggerated RelA activation on the part of blood outgrowth endothelial cells from the at-risk subjects in response to stimulation with interleukin-1β/tumor necrosis factor. We conclude that the pathobiology of circle of Willis disease in the child with sickle cell anemia predominantly involves inflammation biology, which could reflect differences in genetically determined endothelial biology that account for differing host responses to inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Arterial access for sickle stroke predictors Mary E. Fabry Blood 2008 111: 3310-3311. [Full Text] [PDF] This article has been cited by other articles: S. J. Hasstedt, I. D. Bezemer, P. W. Callas, C. Y. Vossen, W. Trotman, R. P. Hebbel, C. Demers, F. R. Rosendaal, and E. G. Bovill Cell adhesion molecule 1: a novel risk factor for venous thrombosis Blood, October 1, 2009; 114(14): 3084 - 3091. [Abstract] [Full Text] [PDF]

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