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Blood, 4 June 2009, Vol. 113, No. 23, pp. 6015-6022. Prepublished online as a Blood First Edition Paper on April 6, 2009; DOI 10.1182/blood-2008-10-186650. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-10-186650v1 113/23/6015    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 CrossRef Google Scholar Articles by Kisucka, J. Articles by Wagner, D. D. PubMed PubMed Citation Articles by Kisucka, J. Articles by Wagner, D. D. Related Collections Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis Janka Kisucka1,2, Anil K. Chauhan1,2, Bing-Qiao Zhao1,2, Ian S. Patten1, Ayce Yesilaltay3, Monty Krieger3, and Denisa D. Wagner1,2 1 Immune Disease Institute and 2 Department of Pathology, Harvard Medical School, Boston, MA; and 3 Department of Biology, Massachusetts Institute of Technology, Cambridge Cerebrovascular and cardiovascular diseases are a major cause of morbidity and mortality. Soluble P-selectin (sP-selectin) is a biomarker for platelet/endothelial activation and is considered a risk factor for vascular disease. sP-selectin enhances procoagulant activity by inducing leukocyte-derived microparticle production and promotes activation of leukocyte integrins. However, it is not known whether it directly contributes to vascular complications. We investigated the effect of increased levels of sP-selectin on blood-brain barrier (BBB) function, stroke outcome, and atherosclerosis by comparing wild-type mice with P-selCT/CT mice in which the endogenous P-selectin gene was replaced with a mutant that produces abnormally high plasma levels of sP-selectin. P-selCT/CT mice presented several abnormalities, including (1) higher BBB permeability, with 25% of the animals showing differential permeability between the right and left hemispheres; (2) altered social behavior with increased aggression; (3) larger infarcts in the middle cerebral artery occlusion ischemic stroke model; and (4) increased susceptibility to atherosclerotic, macrophage-rich lesion development in both male and female mice on the apoE–/– genetic background. Thus, elevated sP-selectin is not only a biomarker for vascular disease, but also may contribute directly to atherosclerosis and cerebrovascular complications. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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