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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4261-4267. Prepublished online as a Blood First Edition Paper on September 18, 2007; DOI 10.1182/blood-2007-04-086611. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-04-086611v1 110/13/4261    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 Vicente, C. P. Articles by Tollefsen, D. M. Search for Related Content PubMed PubMed Citation Articles by Vicente, C. P. Articles by Tollefsen, D. M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Accelerated atherogenesis and neointima formation in heparin cofactor II–deficient mice Cristina P. Vicente1, Li He2, and Douglas M. Tollefsen2 1 Department of Cellular Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas-São Paulo, Brazil; and 2 Hematology Division, Washington University Medical School, St Louis, MO Heparin cofactor II (HCII) is a plasma protein that inhibits thrombin when bound to dermatan sulfate or heparin. HCII-deficient mice are viable and fertile but rapidly develop thrombosis of the carotid artery after endothelial injury. We now report the effects of HCII deficiency on atherogenesis and neointima formation. HCII-null or wild-type mice, both on an apolipoprotein E–null background, were fed an atherogenic diet for 12 weeks. HCII-null mice developed plaque areas in the aortic arch approximately 64% larger than wild-type mice despite having similar plasma lipid and glucose levels. Neointima formation was induced by mechanical dilation of the common carotid artery. Thrombin activity, determined by hirudin binding or chromogenic substrate hydrolysis within 1 hour after injury, was higher in the arterial walls of HCII-null mice than in wild-type mice. After 3 weeks, the median neointimal area was 2- to 3-fold greater in HCII-null than in wild-type mice. Dermatan sulfate administered intravenously within 48 hours after injury inhibited neointima formation in wild-type mice but had no effect in HCII-null mice. Heparin did not inhibit neointima formation. We conclude that HCII deficiency promotes atherogenesis and neointima formation and that treatment with dermatan sulfate reduces neointima formation in an HCII-dependent manner. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. He, T. K. Giri, C. P. Vicente, and D. M. Tollefsen Vascular dermatan sulfate regulates the antithrombotic activity of heparin cofactor II Blood, April 15, 2008; 111(8): 4118 - 4125. [Abstract] [Full Text] [PDF]

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