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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4137-4144.
Prepublished online as a Blood First Edition Paper on February 15, 2008; DOI 10.1182/blood-2007-07-101733.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Mice lacking the extracellular matrix protein MAGP1 display delayed thrombotic occlusion following vessel injury

Claudio C. Werneck1,*, Cristina P. Vicente2,*, Justin S. Weinberg3, Adrian Shifren4, Richard A. Pierce4, Thomas J. Broekelmann3, Douglas M. Tollefsen4, and Robert P. Mecham3

Departments of1 Biochemistry and 2 Cell Biology, Institute of Biology, State University of Campinas-UNICAMP, Campinas, Brazil; and Departments of3 Cell Biology and Physiology and 4 Medicine, Washington University School of Medicine, St Louis, MO

Mice lacking the extracellular matrix protein microfibril-associated glycoprotein-1 (MAGP1) display delayed thrombotic occlusion of the carotid artery following injury as well as prolonged bleeding from a tail vein incision. Normal occlusion times were restored when recombinant MAGP1 was infused into deficient animals prior to vessel wounding. Blood coagulation was normal in these animals as assessed by activated partial thromboplastin time and prothrombin time. Platelet number was lower in MAGP1-deficient mice, but the platelets showed normal aggregation properties in response to various agonists. MAGP1 was not found in normal platelets or in the plasma of wild-type mice. In ligand blot assays, MAGP1 bound to fibronectin, fibrinogen, and von Willebrand factor, but von Willebrand factor was the only protein of the 3 that bound to MAGP1 in surface plasmon resonance studies. These findings show that MAGP1, a component of microfibrils and vascular elastic fibers, plays a role in hemostasis and thrombosis.


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