|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 April 2002, Vol. 99, No. 7, pp. 2455-2458
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Impact of antithrombin deficiency in thrombogenesis:
lipopolysaccharide and stress-induced thrombus formation in
heterozygous antithrombin-deficient mice
Masamitsu Yanada,
Tetsuhito Kojima,
Kazuhiro Ishiguro,
Yukiko Nakayama,
Koji Yamamoto,
Tadashi Matsushita,
Kenji Kadomatsu,
Masahiko Nishimura,
Takashi Muramatsu, and
Hidehiko Saito
From the First Department of Internal Medicine,
Department of Biochemistry, and Institute for Laboratory Animal
Research, Nagoya University School of Medicine, and the Department of
Medical Technology, Nagoya University School of Health Sciences, Nagoya
National Hospital, Japan.
Antithrombin (AT) deficiency is an autosomal disorder associated
with venous thromboembolism. However, a diagnosis of homozygous AT
deficiency is seldom made. Most patients are heterozygous and have
approximately 50% AT activities, and they are at higher risk for the
development of thromboembolism. Through gene targeting we generated
AT-deficient mice and previously reported that completely AT-deficient
mice could not survive the prenatal period because of extensive
thrombosis in the myocardium and liver sinusoids. In contrast,
heterozygous AT-deficient mice with 50% AT activities have not shown
spontaneous thromboembolic episodes. To demonstrate a thrombotic
tendency in heterozygous AT deficiency, we challenged heterozygous
AT-deficient mice (AT+/ mice) with the administration of
lipopolysaccharide (LPS) or with restraint stress by immobilization. LPS injection markedly induced fibrin deposition in the kidney glomeruli, myocardium, and liver sinusoids in AT+/ mice
compared with wild-type mice (AT+/+ mice). Restraint stress
tests were performed by placing mice in 50-mL conical centrifuge tubes
for 20 hours. Fibrin deposition was observed in the kidney of
AT+/+ and AT+/ mice, but AT+/
mice exhibited more extensive fibrin deposition than
AT+/+ mice. After prophylactic administration of human AT
concentrates to increase plasma AT activities of AT+/ mice, LPS-induced fibrin deposition was effectively prevented. These results suggest that heterozygous AT deficiency is significantly associated with a tendency toward thrombosis formation in the kidney.
The AT+/ mouse thus is a useful model for studying the effect of environmental or genetic risk factors on thrombogenesis.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Fukuda, Y. Honda, C. Matsumoto, N. Sugiyama, T. Matsushita, M. Yanada, Y. Morishima, and T. Shibano
Impact of Antithrombin Deficiency on Efficacies of DU-176b, a Novel Orally Active Direct Factor Xa Inhibitor, and Antithrombin Dependent Anticoagulants, Fondaparinux and Heparin.
Blood (ASH Annual Meeting Abstracts),
November 16, 2005;
106(11):
1874 - 1874.
[Abstract]
|
|
|
|
|
|
|
J. Corral, J. Yelamos, D. Hernandez-Espinosa, Y. Monreal, R. Mota, I. Arcas, A. Minano, P. Parrilla, and V. Vicente
Role of Lipopolysaccharide and Cecal Ligation and Puncture on Blood Coagulation and Inflammation in Sensitive and Resistant Mice Models
Am. J. Pathol.,
April 1, 2005;
166(4):
1089 - 1098.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Schabbauer, M. Tencati, B. Pedersen, R. Pawlinski, and N. Mackman
PI3K-Akt Pathway Suppresses Coagulation and Inflammation in Endotoxemic Mice
Arterioscler. Thromb. Vasc. Biol.,
October 1, 2004;
24(10):
1963 - 1969.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-i. Aihara, H. Azuma, M. Akaike, Y. Ikeda, M. Yamashita, T. Sudo, H. Hayashi, Y. Yamada, F. Endoh, M. Fujimura, et al.
Disruption of Nuclear Vitamin D Receptor Gene Causes Enhanced Thrombogenicity in Mice
J. Biol. Chem.,
August 20, 2004;
279(34):
35798 - 35802.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Pawlinski, B. Pedersen, G. Schabbauer, M. Tencati, T. Holscher, W. Boisvert, P. Andrade-Gordon, R. D. Frank, and N. Mackman
Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia
Blood,
February 15, 2004;
103(4):
1342 - 1347.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Dewerchin, J.-P. Herault, G. Wallays, M. Petitou, P. Schaeffer, L. Millet, J. I. Weitz, L. Moons, D. Collen, P. Carmeliet, et al.
Life-Threatening Thrombosis in Mice With Targeted Arg48-to-Cys Mutation of the Heparin-Binding Domain of Antithrombin
Circ. Res.,
November 28, 2003;
93(11):
1120 - 1126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Levi, J. Dorffler-Melly, P. Reitsma, H. Buller, S. Florquin, T. van der Poll, and P. Carmeliet
Aggravation of endotoxin-induced disseminated intravascular coagulation and cytokine activation in heterozygous protein-C-deficient mice
Blood,
June 15, 2003;
101(12):
4823 - 4827.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. C. Aird
The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome
Blood,
May 15, 2003;
101(10):
3765 - 3777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Yamamoto, T. Shimokawa, H. Yi, K.-i. Isobe, T. Kojima, D. J. Loskutoff, and H. Saito
Aging and obesity augment the stress-induced expression of tissue factor gene in the mouse
Blood,
December 1, 2002;
100(12):
4011 - 4018.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
