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

• Published in: Blood 2008-04, Vol.111 (8), p.4137-4144
• Main Authors: Werneck, Claudio C., Vicente, Cristina P., Weinberg, Justin S., Shifren, Adrian, Pierce, Richard A., Broekelmann, Thomas J., Tollefsen, Douglas M., Mecham, Robert P.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bleeding Time; Blood Coagulation - drug effects; Blood Platelets - drug effects; Blood Pressure - drug effects; Carotid Arteries - drug effects; Carotid Arteries - pathology; Carotid Arteries - physiopathology; Cattle; Contractile Proteins - deficiency; Contractile Proteins - metabolism; Extracellular Matrix Proteins - deficiency; Extracellular Matrix Proteins - metabolism; Fibrinogen - metabolism; Fibronectins - metabolism; Hematologic and hematopoietic diseases; Hemostasis, Thrombosis, and Vascular Biology; Humans; Immunohistochemistry; Injections; Medical sciences; Mice; Mice, Inbred C57BL; Platelet Function Tests; Protein Binding - drug effects; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; RNA Splicing Factors; Surface Plasmon Resonance; Thrombosis - pathology; von Willebrand Factor - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-07-101733

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.