Journal of the American Society of Nephrology
2007 JASN IMPACT FACTOR 7.111 HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP 
    advanced
CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Eitzman, D. T.
Right arrow Articles by Shayman, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eitzman, D. T.
Right arrow Articles by Shayman, J. A.
J Am Soc Nephrol 14:298-302, 2003
© 2003 American Society of Nephrology

Fabry Disease in Mice Is Associated With Age-Dependent Susceptibility to Vascular Thrombosis

Daniel T. Eitzman*, Peter F. Bodary*, Yuechun Shen*, Christian G. Khairallah*, Susan R. Wild{dagger}, Akira Abe{dagger}, Jacqueline Shaffer-Hartman{dagger} and James A. Shayman{dagger}

Divisions of *Cardiology and {dagger}Nephrology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan.

Correspondence to Dr. Daniel T. Eitzman, University of Michigan Medical Center, 7301 MSRB III, 1150 Medical Center Dr., Ann Arbor, MI 49109-0644. Phone: 734-763-7838; Fax: 734-936-2641;

ABSTRACT. Fabry disease is an X-linked lysosomal storage disorder due to deficiency of {alpha}-galactosidase A (GLA) activity that results in the widespread accumulation of neutral glycosphingolipids. Renal failure, neuropathy, premature myocardial infarction, and stroke occur in patients with this condition primarily due to deposition of glycosphingolipids in vascular endothelial cells. The clinical consequences of Fabry disease suggest that vascular thrombosis may play a prominent role in the pathogenesis of this disease; however, the vasculopathy associated with Fabry disease has not been extensively studied. To determine if mice genetically deficient in Gla are susceptible to vascular thrombosis, a photochemical carotid injury model was used to induce occlusive thrombosis. In this model, Gla-/0 mice displayed a progressive age-dependent shortening of the time to occlusive thrombosis after vascular injury that correlated with progressive accumulation of globotriasylceramide (Gb3) in the arterial wall. Bone marrow transplantation from Gla-/0 to Gla+/0 mice and from Gla+/0 to Gla-/0 mice did not change the thrombotic phenotype of the host. These studies reveal a potent vascular prothrombotic phenotype in Gla-deficient mice and suggest that antithrombotic therapies as well as therapies designed to reduce the vascular accumulation of Gb3 may have beneficial effects on thrombotic complications in patients with Fabry disease. E-mail: deitzman@umich.edu




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
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]

Home page
 J. Biol. Chem.Home page
L. Shu and J. A. Shayman
Caveolin-associated Accumulation of Globotriaosylceramide in the Vascular Endothelium of {alpha}-Galactosidase A Null Mice
J. Biol. Chem., July 20, 2007; 282(29): 20960 - 20967.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. F. Moore, M. P. Gelderman, P. A. Ferreira, S. R. Fuhrmann, H. Yi, A. Elkahloun, L. M. Lix, R. O. Brady, R. Schiffmann, and E. Goldin
Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach
PNAS, May 8, 2007; 104(19): 8065 - 8070.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
G. G. Camici, J. Steffel, A. Akhmedov, N. Schafer, J. Baldinger, U. Schulz, K. Shojaati, C. M. Matter, Z. Yang, T. F. Luscher, et al.
Dimethyl Sulfoxide Inhibits Tissue Factor Expression, Thrombus Formation, and Vascular Smooth Muscle Cell Activation: A Potential Treatment Strategy for Drug-Eluting Stents
Circulation, October 3, 2006; 114(14): 1512 - 1521.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
Y. Shen, P. F. Bodary, F. B. Vargas, J. W. Homeister, D. Gordon, K. A. Ostenso, J. A. Shayman, and D. T. Eitzman
{alpha}-Galactosidase A Deficiency Leads to Increased Tissue Fibrin Deposition and Thrombosis in Mice Homozygous for the Factor V Leiden Mutation
Stroke, April 1, 2006; 37(4): 1106 - 1108.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
L. Shu, H. S. Murphy, L. Cooling, and J. A. Shayman
An In Vitro Model of Fabry Disease
J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2636 - 2645.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
D. T. Eitzman, R. J. Westrick, Y. Shen, P. F. Bodary, S. Gu, S. L. Manning, S. L. Dobies, and D. Ginsburg
Homozygosity for Factor V Leiden Leads to Enhanced Thrombosis and Atherosclerosis in Mice
Circulation, April 12, 2005; 111(14): 1822 - 1825.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
P. F. Bodary, Y. Shen, F. B. Vargas, X. Bi, K. A. Ostenso, S. Gu, J. A. Shayman, and D. T. Eitzman
{alpha}-Galactosidase A Deficiency Accelerates Atherosclerosis in Mice With Apolipoprotein E Deficiency
Circulation, February 8, 2005; 111(5): 629 - 632.
[Abstract] [Full Text] [PDF]


HOME CURRENT ISSUE ARCHIVES JASN Express ONLINE SUBMISSION AUTHOR INFO
EDITORIAL BOARD SUBSCRIBE FEEDBACK ALERTS HELP

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673