title: Vitronectin stabilizes thrombi and vessel occlusion but plays a dual role in platelet aggregation.
abstract: The role of vitronectin (Vn) in thrombosis is currently controversial; both inhibitory and supportive roles have been reported. To monitor directly the function of Vn in thrombotic events at the site of vascular injury, we studied Vn-deficient (Vn-/-) and wild-type (WT) control mice with two real-time intravital microscopy thrombosis models. In the mesenteric arteriole model, vessel injury was induced by ferric chloride. We observed unstable thrombi and a significantly greater number of emboli in Vn-/- mice. Vessel occlusion was also delayed and frequent vessel re-opening occurred. In the cremaster muscle arteriole model, vessel injury was induced by a nitrogen dye laser. We observed significantly fewer platelets, lower fibrin content, and unstable fibrin within the thrombi of Vn-/- mice. To define further the role of Vn in thrombus growth, we studied platelet aggregation in vitro. Consistent with our in vivo data, the second wave of thrombin-induced aggregation of gel-filtered platelets was abolished at a low concentration of thrombin in Vn-/- platelets. Interestingly, adenosine diphosphate (ADP)-induced platelet aggregation was significantly increased in Vn-/- platelet-rich plasma (PRP) and this effect was attenuated by adding purified plasma Vn. We also observed increased platelet aggregation induced by shear stress in Vn-/- whole blood. These data demonstrate that Vn is a thrombus stabilizer. However, in contrast to released platelet granule Vn which enhances platelet aggregation, plasma Vn inhibits platelet aggregation.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Reheman
authors.forename: P
authors.initials: P
authors.lastname: Gross
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Allen
authors.forename: V
authors.initials: V
authors.lastname: Leytin
authors.forename: J
authors.initials: J
authors.lastname: Freedman
authors.forename: H
authors.initials: H
authors.lastname: Ni
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002850:Chromatography, Gel; D007834:Lasers; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008853:Microscopy; D009132:Muscles / Q000378:metabolism; D009584:Nitrogen / Q000737:chemistry; D010949:Plasma / Q000378:metabolism; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism*; D019096:Vitronectin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
chemical_list: D019096:Vitronectin; D000244:Adenosine Diphosphate; D013917:Thrombin; D009584:Nitrogen