Mice lacking the extracellular matrix protein MAGP1 display delayed thrombotic occlusion following vessel injury.
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.
Werneck
Claudio C
CC
Department of Biochemistry, Institute of Biology, State University of Campinas-UNICAMP, Campinas, Brazil.
Vicente
Cristina P
CP
Weinberg
Justin S
JS
Shifren
Adrian
A
Pierce
Richard A
RA
Broekelmann
Thomas J
TJ
Tollefsen
Douglas M
DM
Mecham
Robert P
RP
D000818:Animals; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D002417:Cattle; D003285:Contractile Proteins / Q000172:deficiency* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007267:Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D010979:Platelet Function Tests; D011485:Protein Binding / Q000187:drug effects; D000072260:RNA Splicing Factors; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D020349:Surface Plasmon Resonance; D013927:Thrombosis / Q000473:pathology*; D014841:von Willebrand Factor / Q000378:metabolism
D003285:Contractile Proteins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D000072260:RNA Splicing Factors; D011994:Recombinant Proteins; C016598:microfibrillar protein; D014841:von Willebrand Factor; D005340:Fibrinogen