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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2237-2243. Prepublished online as a Blood First Edition Paper on June 27, 2006; DOI 10.1182/blood-2006-02-005991. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-005991v1 108/7/2237    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 Dayal, S. Articles by Lentz, S. R Search for Related Content PubMed PubMed Citation Articles by Dayal, S. Articles by Lentz, S. R Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 28, 2006 Accepted May 23, 2006 Enhanced susceptibility to arterial thrombosis in a murine model of hyperhomocysteinemia Sanjana Dayal, Katina M Wilson, Lorie Leo, Erland Arning, Teodoro Bottiglieri, and Steven R Lentz* Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA Baylor Institute of Metabolic Disease, Dallas, Texas, USA * Corresponding author; email: steven-lentz{at}uiowa.edu. Hyperhomocysteinemia is a risk factor for thrombosis, but the mechanisms are not well defined. We tested the hypothesis that hyperhomocysteinemia accelerates arterial thrombosis in mice. Mice heterozygous for a targeted disruption of the cystathionine -synthase gene (Cbs+/-) and wild type littermates (Cbs+/+) were fed either a control diet or a high methionine/low folate (HM/LF) diet for 6-8 months to produce graded hyperhomocysteinemia. The time to occlusion of the carotid artery after photochemical injury was shortened by >50% in Cbs+/+ or Cbs+/- mice fed the HM/LF diet (P<0.001 vs. control diet). Carotid artery thrombosis was not accelerated in mice deficient in endothelial nitric oxide synthase (Nos3), which suggests that decreased endothelium-derived nitric oxide is not a sufficient mechanism for enhancement of thrombosis. Cbs+/+ and Cbs+/- mice fed the HM/LF diet had elevated levels of reactive oxygen species in the carotid artery, increased aortic expression of the NADPH oxidase catalytic subunit, Nox4, and decreased activation of anticoagulant protein C in the aorta (P<0.05 vs. control diet). We conclude that hyperhomocysteinemia enhances susceptibility to arterial thrombosis through a mechanism that is not caused by loss of endothelium-derived nitric oxide but may involve oxidative stress and impairment of the protein C anticoagulant pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Hyperhomocysteinemia: the protein C pathway to thrombosis Diane E. Handy Blood 2006 108: 2137-2138. [Full Text] [PDF] This article has been cited by other articles: A. Brill, A. K. Chauhan, M. Canault, M. T. Walsh, W. Bergmeier, and D. D. Wagner Oxidative stress activates ADAM17/TACE and induces its target receptor shedding in platelets in a p38-dependent fashion Cardiovasc Res, October 1, 2009; 84(1): 137 - 144. [Abstract] [Full Text] [PDF] U. Sen, P. Basu, O. A. Abe, S. Givvimani, N. Tyagi, N. Metreveli, K. S. Shah, J. C. Passmore, and S. C. Tyagi Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure Am J Physiol Renal Physiol, August 1, 2009; 297(2): F410 - F419. [Abstract] [Full Text] [PDF] S. Dayal and S. R. Lentz Murine Models of Hyperhomocysteinemia and Their Vascular Phenotypes Arterioscler Thromb Vasc Biol, September 1, 2008; 28(9): 1596 - 1605. [Abstract] [Full Text] [PDF] S. Dayal, R. N. Rodionov, E. Arning, T. Bottiglieri, M. Kimoto, D. J. Murry, J. P. Cooke, F. M. Faraci, and S. R. Lentz Tissue-specific downregulation of dimethylarginine dimethylaminohydrolase in hyperhomocysteinemia Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H816 - H825. [Abstract] [Full Text] [PDF] S. Chrissobolis, S. P. Didion, D. A. Kinzenbaw, L. I. Schrader, S. Dayal, S. R. Lentz, and F. M. Faraci Glutathione Peroxidase-1 Plays a Major Role in Protecting Against Angiotensin II-Induced Vascular Dysfunction Hypertension, April 1, 2008; 51(4): 872 - 877. [Abstract] [Full Text] [PDF] U. Sen, N. Tyagi, M. Kumar, K. S. Moshal, W. E. Rodriguez, and S. C. Tyagi Cystathionine- -synthase gene transfer and 3-deazaadenosine ameliorate inflammatory response in endothelial cells Am J Physiol Cell Physiol, December 1, 2007; 293(6): C1779 - C1787. [Abstract] [Full Text] [PDF] R. J. Westrick, M. E. Winn, and D. T. Eitzman Murine Models of Vascular Thrombosis Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2079 - 2093. [Abstract] [Full Text] [PDF] S. M. Colgan and R. C. Austin Homocysteinylation of Metallothionein Impairs Intracellular Redox Homeostasis: The Enemy Within! Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 8 - 11. [Full Text] [PDF] K. M. Wilson, R. B. McCaw, L. Leo, E. Arning, S. Lhotak, T. Bottiglieri, R. C. Austin, and S. R. Lentz Prothrombotic Effects of Hyperhomocysteinemia and Hypercholesterolemia in ApoE-Deficient Mice Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 233 - 240. [Abstract] [Full Text] [PDF]

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