|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 6 (March 15), 1999:
pp. 1825-1830
RAPID COMMUNICATION
Vitronectin Inhibits the Thrombotic Response to Arterial Injury in Mice
William P. Fay,
Andrew C. Parker,
Maria N. Ansari,
Xianxian Zheng, and
David Ginsburg
From the Departments of Internal Medicine and Human Genetics and the
Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI.
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 minutes
v 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 +/+ and
VN / 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 of
VN +/+ 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.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. S. Woulfe, J. K. Lilliendahl, S. August, L. Rauova, M. A. Kowalska, M. Abrink, G. Pejler, J. G. White, and B. P. Schick
Serglycin proteoglycan deletion induces defects in platelet aggregation and thrombus formation in mice
Blood,
April 1, 2008;
111(7):
3458 - 3467.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Westrick, M. E. Winn, and D. T. Eitzman
Murine Models of Vascular Thrombosis
Arterioscler Thromb Vasc Biol,
October 1, 2007;
27(10):
2079 - 2093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. J.H. Sachs and B. Nieswandt
In Vivo Thrombus Formation in Murine Models
Circ. Res.,
April 13, 2007;
100(7):
979 - 991.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Kannemeier, A. Shibamiya, F. Nakazawa, H. Trusheim, C. Ruppert, P. Markart, Y. Song, E. Tzima, E. Kennerknecht, M. Niepmann, et al.
Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation
PNAS,
April 10, 2007;
104(15):
6388 - 6393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. V. Denis and D. D. Wagner
Platelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis
Arterioscler Thromb Vasc Biol,
April 1, 2007;
27(4):
728 - 739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Strassel, C. Nonne, A. Eckly, T. David, C. Leon, M. Freund, J.-P. Cazenave, C. Gachet, and F. Lanza
Decreased Thrombotic Tendency in Mouse Models of the Bernard-Soulier Syndrome
Arterioscler Thromb Vasc Biol,
January 1, 2007;
27(1):
241 - 247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Dubois, L. Panicot-Dubois, G. Merrill-Skoloff, B. Furie, and B. C. Furie
Glycoprotein VI-dependent and -independent pathways of thrombus formation in vivo
Blood,
May 15, 2006;
107(10):
3902 - 3906.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Iafrati, O. Vitseva, K. Tanriverdi, P. Blair, S. Rex, S. Chakrabarti, S. Varghese, and J. E. Freedman
Compensatory mechanisms influence hemostasis in setting of eNOS deficiency
Am J Physiol Heart Circ Physiol,
April 1, 2005;
288(4):
H1627 - H1632.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ekmekci, O. B. Ekmekci, H. Sonmez, Z. Ozturk, N. Domanic, and E. Kokoglu
Evaluation of Fibronectin, Vitronectin, and Leptin Levels in Coronary Artery Disease: Impacts on Thrombosis and Thrombolysis
Clinical and Applied Thrombosis/Hemostasis,
January 1, 2005;
11(1):
63 - 70.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Y.-P. Wu, H. J. Bloemendal, E. E. Voest, T. Logtenberg, P. G. de Groot, M. F. B. G. Gebbink, and H. C. de Boer
Fibrin-incorporated vitronectin is involved in platelet adhesion and thrombus formation through homotypic interactions with platelet-associated vitronectin
Blood,
August 15, 2004;
104(4):
1034 - 1041.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Kerlin, B. C. Cooley, B. H. Isermann, I. Hernandez, R. Sood, M. Zogg, S. B. Hendrickson, M. W. Mosesson, S. Lord, and H. Weiler
Cause-effect relation between hyperfibrinogenemia and vascular disease
Blood,
March 1, 2004;
103(5):
1728 - 1734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. He, L. K. Pappan, D. G. Grenache, Z. Li, D. M. Tollefsen, S. A. Santoro, and M. M. Zutter
The contributions of the {alpha}2{beta}1 integrin to vascular thrombosis in vivo
Blood,
November 15, 2003;
102(10):
3652 - 3657.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Kufrin, D. E. Eslin, K. Bdeir, J.-C. Murciano, A. Kuo, M. A. Kowalska, J. L. Degen, B. S. Sachais, D. B. Cines, and M. Poncz
Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets
Blood,
August 1, 2003;
102(3):
926 - 933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Ni, P. S. T. Yuen, J. M. Papalia, J. E. Trevithick, T. Sakai, R. Fassler, R. O. Hynes, and D. D. Wagner
Plasma fibronectin promotes thrombus growth and stability in injured arterioles
PNAS,
March 4, 2003;
100(5):
2415 - 2419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Massberg, M. Gawaz, S. Gruner, V. Schulte, I. Konrad, D. Zohlnhofer, U. Heinzmann, and B. Nieswandt
A Crucial Role of Glycoprotein VI for Platelet Recruitment to the Injured Arterial Wall In Vivo
J. Exp. Med.,
January 6, 2003;
197(1):
41 - 49.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. MAZZUCATO, M. R. COZZI, P. PRADELLA, D. PERISSINOTTO, A. MALMSTROM, M. MORGELIN, P. SPESSOTTO, A. COLOMBATTI, L. DE MARCO, and R. PERRIS
Vascular PG-M/versican variants promote platelet adhesion at low shear rates and cooperate with collagens to induce aggregation
FASEB J,
December 1, 2002;
16(14):
1903 - 1916.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Chavakis, N. Boeckel, S. Santoso, R. Voss, I. Isordia-Salas, R. A. Pixley, E. Morgenstern, R. W. Colman, and K. T. Preissner
Inhibition of Platelet Adhesion and Aggregation by a Defined Region (Gly-486-Lys-502) of High Molecular Weight Kininogen
J. Biol. Chem.,
June 21, 2002;
277(26):
23157 - 23164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Podor, S. Campbell, P. Chindemi, D. M. Foulon, D. H. Farrell, P. D. Walton, J. I. Weitz, and C. B. Peterson
Incorporation of Vitronectin into Fibrin Clots. EVIDENCE FOR A BINDING INTERACTION BETWEEN VITRONECTIN AND gamma A/gamma ' FIBRINOGEN
J. Biol. Chem.,
February 22, 2002;
277(9):
7520 - 7528.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Weiler, V. Lindner, B. Kerlin, B. H. Isermann, S. B. Hendrickson, B. C. Cooley, D. A. Meh, M. W. Mosesson, N. W. Shworak, M. J. Post, et al.
Characterization of a Mouse Model for Thrombomodulin Deficiency
Arterioscler Thromb Vasc Biol,
September 1, 2001;
21(9):
1531 - 1537.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Konstantinides, K. Schafer, T. Thinnes, and D. J. Loskutoff
Plasminogen Activator Inhibitor-1 and Its Cofactor Vitronectin Stabilize Arterial Thrombi After Vascular Injury in Mice
Circulation,
January 30, 2001;
103(4):
576 - 583.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Chavakis, S. M. Kanse, F. Lupu, H.-P. Hammes, W. Muller-Esterl, R. A. Pixley, R. W. Colman, and K. T. Preissner
Different mechanisms define the antiadhesive function of high molecular weight kininogen in integrin- and urokinase receptor-dependent interactions
Blood,
July 15, 2000;
96(2):
514 - 522.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. T. Eitzman, R. J. Westrick, Z. Xu, J. Tyson, and D. Ginsburg
Hyperlipidemia Promotes Thrombosis After Injury to Atherosclerotic Vessels in Apolipoprotein E-Deficient Mice
Arterioscler Thromb Vasc Biol,
July 1, 2000;
20(7):
1831 - 1834.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kawasaki, M. Dewerchin, H. R. Lijnen, J. Vermylen, and M. F. Hoylaerts
Vascular release of plasminogen activator inhibitor-1 impairs fibrinolysis during acute arterial thrombosis in mice
Blood,
July 1, 2000;
96(1):
153 - 160.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. T. Eitzman, R. J. Westrick, E. G. Nabel, and D. Ginsburg
Plasminogen activator inhibitor-1 and vitronectin promote vascular thrombosis in mice
Blood,
January 15, 2000;
95(2):
577 - 580.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. P. Francois, K. T. Preissner, M. Herrmann, R. P. Haugland, P. Vaudaux, D. P. Lew, and K.-H. Krause
Vitronectin Interaction with Glycosaminoglycans. KINETICS, STRUCTURAL DETERMINANTS, AND ROLE IN BINDING TO ENDOTHELIAL CELLS
J. Biol. Chem.,
December 31, 1999;
274(53):
37611 - 37619.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. M. Faraci and C. D. Sigmund
Vascular Biology in Genetically Altered Mice : Smaller Vessels, Bigger Insight
Circ. Res.,
December 3, 1999;
85(12):
1214 - 1225.
[Full Text]
[PDF]
|
|
|
|
|
