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Vitronectin stabilizes thrombi and vessel occlusion but plays a dual role in platelet aggregation
Author(s) -
REHEMAN A.,
GROSS P.,
YANG H.,
CHEN P.,
ALLEN D.,
LEYTIN V.,
FREEDMAN J.,
NI H.
Publication year - 2005
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2005.01217.x
Subject(s) - vitronectin , platelet aggregation , platelet , dual (grammatical number) , occlusion , chemistry , platelet adhesiveness , cardiology , biophysics , microbiology and biotechnology , medicine , integrin , biology , receptor , philosophy , linguistics
Summary. 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.