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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 (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 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 Milbauer, L. C. Articles by Hebbel, R. P. Search for Related Content PubMed PubMed Citation Articles by Milbauer, L. C. Articles by Hebbel, R. P. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 25, 2007 Accepted November 2, 2007 Genetic endothelial systems biology of sickle stroke risk Liming Chang Milbauer, Peng Wei, Judy Enenstein, Aixiang Jiang, Cheryl A. Hillery, J. Paul Scott, Stephen C. Nelson, Vidya Bodempudi, James N. Topper, Ruey-Bing Yang, Betsy Hirsch, Wei Pan, and Robert P. Hebbel* Vascular Biology Center and Division of Hematology-Oncology-Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, United States Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States Blood Research Institute, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI, United States Minneapolis Children's' Hospital and Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, United States Millennium Pharmaceuticals, San Francisco, CA, United States Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, United States * Corresponding author; email: hebbe001{at}umn.edu. Genetic differences in endothelial biology could underlie development of phenotypic heterogeneity amongst individuals afflicted with vascular diseases. We obtained BOEC (blood outgrowth endothelial cells) from 20 subjects with sickle cell anemia (age 4-19) shown to be either at-risk (n=11) or not-at-risk (n=9) for ischemic stroke due to, respectively, having or not having occlusive disease at the Circle of Willis (CoW). Gene expression profiling identified no significant single gene differences between the two groups, as expected. However, analysis of Biological Systems Scores, using gene sets that were pre-determined to survey each of nine biological systems, showed that only changes in inflammation signaling are characteristic of the at-risk subjects, as supported by multiple statistical approaches. Correspondingly, subsequent biological testing showed significantly exaggerated RelA activation on the part of BOEC from the at-risk subjects in response to stimulation with IL1/TNF. We conclude that the pathobiology of CoW disease in the sickle child 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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