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Vitronectin Inhibits the Thrombotic Response to Arterial Injury in Mice
- Source :
- Blood. 93:1825-1830
- Publication Year :
- 1999
- Publisher :
- American Society of Hematology, 1999.
-
Abstract
- Vitronectin (VN) binds to plasminogen activator inhibitor-1 (PAI-1) and integrins and may play an important role in the vascular response to injury by regulating fibrinolysis and cell migration. However, the role of VN in the earliest response to vascular injury, thrombosis, is not well characterized. The purpose of this study was to test the hypothesis that variation in vitronectin expression alters the thrombotic response to arterial injury in mice. Ferric chloride (FeCl3) injury was used to induce platelet-rich thrombi in mouse carotid arteries. Wild-type (VN +/+, n = 14) and VN-deficient (VN −/−, n = 15) mice, matched for age and gender, were studied. Time to occlusion after FeCl3 injury was determined by application of a Doppler flowprobe to the carotid artery. Occlusion times of VN −/− mice were significantly shorter than those of VN +/+ mice (6.0 ± 1.2 minutesv 17.8 ± 2.3 minutes, respectively, P < .001). Histologic analysis of injured arterial segments showed that thrombi from VN +/+ and VN −/− mice consisted of dense platelet aggregates. In vitro studies of murine VN +/+ andVN −/− platelets showed no significant differences in ADP-induced aggregation, but a trend towards increased thrombin-induced aggregation in VN −/− platelets. Purified, denatured VN inhibited thrombin-induced platelet aggregation, whereas native VN did not. Thrombin times of plasma from VN −/− mice (20.5 ± 2.1 seconds, n = 4) were significantly shorter than those ofVN +/+ mice (34.2 ± 6.7 seconds, n = 4, P < .01), and the addition of purified VN to VN −/− plasma prolonged the thrombin time into the normal range, suggesting that VN inhibits thrombin-fibrinogen interactions. PAI-1-deficient mice (n = 6) did not demonstrate significantly enhanced arterial thrombosis compared with wild-type mice (n = 6), excluding a potential indirect antithrombin function of VN mediated by interactions with PAI-1 as an explanation for the accelerated thrombosis observed in VN−/− mice. These results suggest that vitronectin plays a previously unappreciated antithrombotic role at sites of arterial injury and that this activity may be mediated, at least in part, by inhibiting platelet-platelet interactions and/or thrombin procoagulant activity.
- Subjects :
- medicine.medical_specialty
Pathology
biology
medicine.diagnostic_test
business.industry
Immunology
Cell Biology
Hematology
Thrombin time
Fibrinogen
Biochemistry
chemistry.chemical_compound
Thrombin
Endocrinology
chemistry
Internal medicine
Plasminogen activator inhibitor-1
medicine
biology.protein
Platelet
Vitronectin
business
Plasminogen activator
Fibrinolytic agent
medicine.drug
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi...........ae00fedf72510fa8f313590c5b76e54a