|
|
 Previous Article | Table of Contents | Next Article 
Shear stress enhances the proteolysis of von Willebrand factor in normal
plasma
HM Tsai, II Sussman and RL Nagel
Division of Hematology, Montefiore Medical Center/Albert Einstein College
of Medicine, Bronx, NY 10467.
While von Willebrand factor (vWF) is secreted from endothelial cells as a
very large polymer, it circulates as a series of multimers that are
reducible to a 225-kD polypeptide and three proteolytic fragments of 189,
176, and 140 kD. Cleavage at the Tyr-842/Met-843 bond of the vWF
polypeptide creates the 140- and 176-kD fragments. In the process of
understanding vWF multimer formation, the role of shear stress in vWF
proteolysis was investigated in this study. A shear-rate-dependent loss of
the largest multimers was observed when normal plasma was perfused through
long capillary tubings achieving shear rates normally encountered in the
circulation. The shear-dependent vWF change was not observed when purified
vWF or normal plasma containing calcium chelator EGTA or EDTA was perfused.
As the large multimers decreased, an increase in the smaller multimers,
including 200- and 350-kD bands, was detected. Elution and immunoblotting
studies with peptide-specific antibodies LJ-7745 and VP-1 showed that the
200-kD band was a dimer of the 140-kD fragment, whereas the 350-kD band was
a dimer of the 176-kD fragment. When analyzed after disulfide bonds were
reduced, sheared plasma showed an increase in the 176- and 140-kD
fragments, but not the 189-kD fragment. Finally, shearing of purified vWF
enhanced its proteolytic cleavage when it was subsequently incubated with
the cryosupernatant fraction of normal plasma or with cathepsin G, a
leukocyte granule serine protease. These results show that shear stress is
capable of enhancing the susceptibility of vWF to proteolytic cleavage. It
promotes vWF proteolysis in normal plasma at a site that generates the
140-kD/176-kD fragments, leading to a decrease in multimer size. Shear
stress might be involved in modulating the size of vWF in the circulation.
Volume 83,
Issue 8,
pp. 2171-2179,
04/15/1994
Copyright © 1994 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Le Tourneau, S. Susen, C. Caron, A. Millaire, S. Marechaux, A.-S. Polge, A. Vincentelli, F. Mouquet, P.-V. Ennezat, N. Lamblin, et al.
Functional Impairment of Von Willebrand Factor in Hypertrophic Cardiomyopathy: Relation to Rest and Exercise Obstruction
Circulation,
October 7, 2008;
118(15):
1550 - 1557.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Di Stasio, S. Lancellotti, F. Peyvandi, R. Palla, P. M. Mannucci, and R. De Cristofaro
Mechanistic Studies on ADAMTS13 Catalysis
Biophys. J.,
September 1, 2008;
95(5):
2450 - 2461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Buzza, J. M. Dyson, H. Choi, E. E. Gardiner, R. K. Andrews, D. Kaiserman, C. A. Mitchell, M. C. Berndt, J.-F. Dong, and P. I. Bird
Antihemostatic Activity of Human Granzyme B Mediated by Cleavage of von Willebrand Factor
J. Biol. Chem.,
August 15, 2008;
283(33):
22498 - 22504.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. E. Hobbs II and J. A. Lopez
Shear elegance: regulation of thrombus growth by shear stress
Blood,
February 1, 2008;
111(3):
972 - 972.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Shim, P. J. Anderson, E. A. Tuley, E. Wiswall, and J. Evan Sadler
Platelet-VWF complexes are preferred substrates of ADAMTS13 under fluid shear stress
Blood,
January 15, 2008;
111(2):
651 - 657.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Zhang, W. Pan, A. H. Rux, B. S. Sachais, and X. L. Zheng
The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow
Blood,
September 15, 2007;
110(6):
1887 - 1894.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Singh, H. Shankaran, M. E. Beauharnois, Z. Xiao, P. Alexandridis, and S. Neelamegham
Solution Structure of Human von Willebrand Factor Studied Using Small Angle Neutron Scattering
J. Biol. Chem.,
December 15, 2006;
281(50):
38266 - 38275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. A. Hassenpflug, U. Budde, T. Obser, D. Angerhaus, E. Drewke, S. Schneppenheim, and R. Schneppenheim
Impact of mutations in the von Willebrand factor A2 domain on ADAMTS13-dependent proteolysis
Blood,
March 15, 2006;
107(6):
2339 - 2345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Tao, Y. Peng, L. Nolasco, S. Cal, C. Lopez-Otin, R. Li, J. L. Moake, J. A. Lopez, and J.-f. Dong
Recombinant CUB-1 domain polypeptide inhibits the cleavage of ULVWF strings by ADAMTS13 under flow conditions
Blood,
December 15, 2005;
106(13):
4139 - 4145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Majerus, P. J. Anderson, and J. E. Sadler
Binding of ADAMTS13 to von Willebrand Factor
J. Biol. Chem.,
June 10, 2005;
280(23):
21773 - 21778.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. T. B. Crawley, J. K. Lam, J. B. Rance, L. R. Mollica, J. S. O'Donnell, and D. A. Lane
Proteolytic inactivation of ADAMTS13 by thrombin and plasmin
Blood,
February 1, 2005;
105(3):
1085 - 1093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kokame, M. Matsumoto, Y. Fujimura, and T. Miyata
VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13
Blood,
January 15, 2004;
103(2):
607 - 612.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-f. Dong, J. L. Moake, A. Bernardo, K. Fujikawa, C. Ball, L. Nolasco, J. A. Lopez, and M. A. Cruz
ADAMTS-13 Metalloprotease Interacts with the Endothelial Cell-derived Ultra-large von Willebrand Factor
J. Biol. Chem.,
August 8, 2003;
278(32):
29633 - 29639.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Vincentelli, S. Susen, T. Le Tourneau, I. Six, O. Fabre, F. Juthier, A. Bauters, C. Decoene, J. Goudemand, A. Prat, et al.
Acquired von Willebrand Syndrome in Aortic Stenosis
N. Engl. J. Med.,
July 24, 2003;
349(4):
343 - 349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Savasan, S.-K. Lee, D. Ginsburg, and H.-M. Tsai
ADAMTS13 gene mutation in congenital thrombotic thrombocytopenic purpura with previously reported normal VWF cleaving protease activity
Blood,
June 1, 2003;
101(11):
4449 - 4451.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-M. Tsai
Advances in the Pathogenesis, Diagnosis, and Treatment of Thrombotic Thrombocytopenic Purpura
J. Am. Soc. Nephrol.,
April 1, 2003;
14(4):
1072 - 1081.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Shankaran, P. Alexandridis, and S. Neelamegham
Aspects of hydrodynamic shear regulating shear-induced platelet activation and self-association of von Willebrand factor in suspension
Blood,
April 1, 2003;
101(7):
2637 - 2645.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-M. Tsai
Platelet Activation and the Formation of the Platelet Plug: Deficiency of ADAMTS13 Causes Thrombotic Thrombocytopenic Purpura
Arterioscler. Thromb. Vasc. Biol.,
March 1, 2003;
23(3):
388 - 396.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Sadler
A new name in thrombosis, ADAMTS13
PNAS,
September 3, 2002;
99(18):
11552 - 11554.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kokame, M. Matsumoto, K. Soejima, H. Yagi, H. Ishizashi, M. Funato, H. Tamai, M. Konno, K. Kamide, Y. Kawano, et al.
Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity
PNAS,
September 3, 2002;
99(18):
11902 - 11907.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Moake
Thrombotic Microangiopathies
N. Engl. J. Med.,
August 22, 2002;
347(8):
589 - 600.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Fujikawa, H. Suzuki, B. McMullen, and D. Chung
Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family
Blood,
September 15, 2001;
98(6):
1662 - 1666.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Veyradier, B. Obert, A. Houllier, D. Meyer, and J.-P. Girma
Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases
Blood,
September 15, 2001;
98(6):
1765 - 1772.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Morigi, M. Galbusera, E. Binda, B. Imberti, S. Gastoldi, A. Remuzzi, C. Zoja, and G. Remuzzi
Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress
Blood,
September 15, 2001;
98(6):
1828 - 1835.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Veyradier, T. Nishikubo, M. Humbert, M. Wolf, O. Sitbon, G. Simonneau, J.-P. Girma, and D. Meyer
Improvement of von Willebrand Factor Proteolysis After Prostacyclin Infusion in Severe Pulmonary Arterial Hypertension
Circulation,
November 14, 2000;
102(20):
2460 - 2462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Furlan and B. Lammle
Haemolytic-uraemic syndrome and thrombotic thrombocytopenic purpura--new insights into underlying biochemical mechanisms
Nephrol. Dial. Transplant.,
August 1, 2000;
15(8):
1112 - 1114.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S L Allford and S J Machin
Current understanding of the pathophysiology of thrombotic thrombocytopenic purpura
J. Clin. Pathol.,
July 1, 2000;
53(7):
497 - 501.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Galbusera, M. Noris, C. Rossi, S. Orisio, J. Caprioli, Z. M. Ruggeri, B. Amadei, P. Ruggenenti, B. Vasile, G. Casari, et al.
Increased Fragmentation of von Willebrand Factor, Due to Abnormal Cleavage of the Subunit, Parallels Disease Activity in Recurrent Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura and Discloses Predisposition in Families
Blood,
July 15, 1999;
94(2):
610 - 620.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. GALBUSERA, A. BENIGNI, S. PARIS, P. RUGGENENTI, C. ZOJA, C. ROSSI, and G. REMUZZI
Unrecognized Pattern of von Willebrand Factor Abnormalities in Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura
J. Am. Soc. Nephrol.,
June 1, 1999;
10(6):
1234 - 1241.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
L. Oleksowicz, N. Bhagwati, and M. DeLeon-Fernandez
Deficient Activity of von Willebrand's Factor-cleaving Protease in Patients with Disseminated Malignancies
Cancer Res.,
May 1, 1999;
59(9):
2244 - 2250.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-M. Tsai and E. C.-Y. Lian
Antibodies to von Willebrand Factor-Cleaving Protease in Acute Thrombotic Thrombocytopenic Purpura
N. Engl. J. Med.,
November 26, 1998;
339(22):
1585 - 1594.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. C. Territo, J. K. Perloff, M. H. Rosove, J. L. Moake, and A. Runge
Acquired Von Willebrand Factor Abnormalities in Adults with Congenital Heart Disease: Dependence Upon Cardiopulmonary Pathophysiological Subtype
Clinical and Applied Thrombosis/Hemostasis,
October 1, 1998;
4(4):
257 - 261.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Furlan, R. Robles, M. Solenthaler, M. Wassmer, P. Sandoz, and B. Lammle
Deficient Activity of von Willebrand Factor-Cleaving Protease in Chronic Relapsing Thrombotic Thrombocytopenic Purpura
Blood,
May 1, 1997;
89(9):
3097 - 3103.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-M. Tsai, I. I. Sussman, D. Ginsburg, H. Lankhof, J. J. Sixma, and R. L. Nagel
Proteolytic Cleavage of Recombinant Type 2A von Willebrand Factor Mutants R834W and R834Q: Inhibition by Doxycycline and by Monoclonal Antibody VP-1
Blood,
March 15, 1997;
89(6):
1954 - 1962.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Kamat, A. D. Michelson, S. E. Benoit, J. L. Moake, D. Rajasekhar, J. D. Hellums, M. H. Kroll, and A. I. Schafer
Fibrinolysis Inhibits Shear Stress–Induced Platelet Aggregation
Circulation,
September 15, 1995;
92(6):
1399 - 1407.
[Abstract]
[Full Text]
|
|
|
|
|
