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Circulation. 1997;95:594-599

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(Circulation. 1997;95:594-599.)
© 1997 American Heart Association, Inc.


Articles

Tissue Factor Modulates the Thrombogenicity of Human Atherosclerotic Plaques

Vincenzo Toschi, MD; Richard Gallo, MD; Maddalena Lettino, MD; John T. Fallon, MD, PhD; S. David Gertz, MD, PhD; Antonio Fernandez-Ortiz, MD, PhD; James H. Chesebro, MD; Lina Badimon, PhD; Yale Nemerson, MD, PhD; Valentin Fuster, MD, PhD; Juan J. Badimon, PhD

the Cardiovascular Biology Research Laboratory, The Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY; Department of Anatomy and Embryology (S.D.G.), The Hebrew University–Hadassah Medical, Jerusalem, Israel; Servicio de Cardiologia (A.F.-O.), Hospital San Carlos Madrid, Spain; and Cardiovascular Research Center (L.B.), CSIC-Hospital Santa Cruz y San Pablo–UAB, Barcelona, Spain.

Correspondence to Juan J. Badimon, PhD, Cardiovascular Biology Research Laboratory, The Cardiovascular Institute (Box 1030), Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029.

Background The thrombogenicity of a disrupted atherosclerotic lesion is dependent on the nature and extent of the plaque components exposed to flowing blood together with local rheology and a variety of systemic factors. We previously reported on the different thrombogenicity of the various types of human atherosclerotic lesions when exposed to flowing blood in a well-characterized perfusion system. This study examines the role of tissue factor in the thrombogenicity of different types of atherosclerotic plaques and their components.

Methods and Results Fifty human arterial segments (5 foam cell–rich, 9 collagen-rich, and 10 lipid-rich atherosclerotic lesions and 26 normal, nonatherosclerotic segments) were exposed to heparinized blood at high shear rate conditions in the Badimon perfusion chamber. The thrombogenicity of the arterial specimens was assessed by 111In-labeled platelets. After perfusion, specimens were stained for tissue factor by use of an in situ binding assay for factor VIIa. Tissue factor in specimens was semiquantitatively assessed on a scale of 0 to 3. Platelet deposition on the lipid-rich atheromatous core was significantly higher than on all other substrates (P=.0002). The lipid-rich core also exhibited the most intense tissue factor staining (3±0.1 arbitrary units) compared with other arterial components. Comparison of all specimens showed a positive correlation between quantitative platelet deposition and tissue factor staining score (r=.35, P<.01).

Conclusions Our results show that tissue factor is present in lipid-rich human atherosclerotic plaques and suggest that it is an important determinant of the thrombogenicity of human atherosclerotic lesions after spontaneous or mechanical plaque disruption.


Key Words: thrombosis • platelets • tissue factor • atherosclerosis • plaque




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Current Perspective on the Role of Apoptosis in Atherothrombotic Disease
Circ. Res., May 25, 2001; 88(10): 998 - 1003.
[Abstract] [Full Text] [PDF]


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Eur Heart J SupplHome page
M. Aikawa and P. Libby
Vascular inflammation and activation: new targets for lipid lowering
Eur. Heart J. Suppl., May 1, 2001; 3(suppl_B): B3 - B11.
[Abstract] [PDF]


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CirculationHome page
J. M. t. Berg, B. A. Hutten, J. C. Kelder, F. W. A. Verheugt, and H. W. T. Plokker
Oral Anticoagulant Therapy During and After Coronary Angioplasty : The Intensity and Duration of Anticoagulation Are Essential to Reduce Thrombotic Complications
Circulation, April 24, 2001; 103(16): 2042 - 2047.
[Abstract] [Full Text] [PDF]


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StrokeHome page
S. Jander, M. Sitzer, A. Wendt, M. Schroeter, M. Buchkremer, M. Siebler, W. Muller, W. Sandmann, and G. Stoll
Expression of Tissue Factor in High-Grade Carotid Artery Stenosis : Association With Plaque Destabilization
Stroke, April 1, 2001; 32(4): 850 - 854.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
P. Zoldhelyi, Z.-Q. Chen, H. S. Shelat, J. M. McNatt, and J. T. Willerson
Local gene transfer of tissue factor pathway inhibitor regulates intimal hyperplasia in atherosclerotic arteries
PNAS, March 27, 2001; 98(7): 4078 - 4083.
[Abstract] [Full Text] [PDF]


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ANN INTERN MEDHome page
U. Rauch, J. I. Osende, V. Fuster, J. J. Badimon, Z. Fayad, and J. H. Chesebro
Thrombus Formation on Atherosclerotic Plaques: Pathogenesis and Clinical Consequences
Ann Intern Med, February 6, 2001; 134(3): 224 - 238.
[Abstract] [Full Text] [PDF]


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CirculationHome page
R. S. Kiesz, P. Buszman, J. L. Martin, E. Deutsch, M. M. Rozek, E. Gaszewska, M. Rewicki, P. Seweryniak, M. Kosmider, and M. Tendera
Local Delivery of Enoxaparin to Decrease Restenosis After Stenting: Results of Initial Multicenter Trial : Polish-American Local Lovenox NIR Assessment Study (The POLONIA Study)
Circulation, January 2, 2001; 103(1): 26 - 31.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
M. Roque, E. D. Reis, V. Fuster, A. Padurean, J. T. Fallon, M. B. Taubman, J. H. Chesebro, and J. J. Badimon
Inhibition of tissue factor reduces thrombus formation and intimal hyperplasia after porcine coronary angioplasty
J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2303 - 2310.
[Abstract] [Full Text] [PDF]


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CirculationHome page
P. R. Moreno, A. M. Murcia, I. F. Palacios, M. N. Leon, V. H. Bernardi, V. Fuster, and J. T. Fallon
Coronary Composition and Macrophage Infiltration in Atherectomy Specimens From Patients With Diabetes Mellitus
Circulation, October 31, 2000; 102(18): 2180 - 2184.
[Abstract] [Full Text] [PDF]


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CirculationHome page
M. M. Kockx, C. Seye, G. R. Y. De Meyer, M. W. M. Knaapen, M. Aikawa, S. J. Voglic, S. Sugiyama, E. Rabkin, P. Libby, M. B. Taubman, et al.
Decreased Apoptosis and Tissue Factor Expression After Lipid Lowering Response
Circulation, September 26, 2000; 102 (13): e99 - e99.
[Full Text] [PDF]


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Eur Heart JHome page
M.E Bertrand, M.L Simoons, K.A.A Fox, L.C Wallentin, C.W Hamm, E McFadden, P.J de Feyter, G Specchia, and W Ruzyllo
Management of acute coronary syndromes: acute coronary syndromes without persistent ST segment elevation. Recommendations of the Task Force of the European Society of Cardiology: Recommendations of the Task Force of the European Society of Cardiology
Eur. Heart J., September 1, 2000; 21(17): 1406 - 1432.
[PDF]


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CirculationHome page
S. Matetzky, S. Tani, S. Kangavari, P. Dimayuga, J. Yano, H. Xu, K.-Y. Chyu, M. C. Fishbein, P. K. Shah, and B. Cercek
Smoking Increases Tissue Factor Expression in Atherosclerotic Plaques : Implications for Plaque Thrombogenicity
Circulation, August 8, 2000; 102(6): 602 - 604.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
A. Tedgui and Z. Mallat
Smooth Muscle Cells : Another Source of Tissue Factor-Containing Microparticles in Atherothrombosis?
Circ. Res., July 21, 2000; 87(2): 81 - 82.
[Full Text] [PDF]


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CirculationHome page
M. Ragni, P. Golino, P. Cirillo, A. Scognamiglio, O. Piro, N. Esposito, C. Battaglia, F. Botticella, P. Ponticelli, L. Ramunno, et al.
Endogenous Tissue Factor Pathway Inhibitor Modulates Thrombus Formation in an In Vivo Model of Rabbit Carotid Artery Stenosis and Endothelial Injury
Circulation, July 4, 2000; 102(1): 113 - 117.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
M. Kjalke, A. Silveira, A. Hamsten, U. Hedner, and M. Ezban
Plasma Lipoproteins Enhance Tissue Factor-Independent Factor VII Activation
Arterioscler Thromb Vasc Biol, July 1, 2000; 20(7): 1835 - 1841.
[Abstract] [Full Text] [PDF]


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CirculationHome page
S. G. Worthley, G. Helft, V. Fuster, Z. A. Fayad, O. J. Rodriguez, A. G. Zaman, J. T. Fallon, and J. J. Badimon
Noninvasive In Vivo Magnetic Resonance Imaging of Experimental Coronary Artery Lesions in a Porcine Model
Circulation, June 27, 2000; 101(25): 2956 - 2961.
[Abstract] [Full Text] [PDF]


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CirculationHome page
Y. Cadroy, J.-P. Bossavy, C. Thalamas, L. Sagnard, K. Sakariassen, and B. Boneu
Early Potent Antithrombotic Effect With Combined Aspirin and a Loading Dose of Clopidogrel on Experimental Arterial Thrombogenesis in Humans
Circulation, June 20, 2000; 101(24): 2823 - 2828.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
S. Kaul and P. K. Shah
Low molecular weight heparin in acute coronary syndrome: evidence for superior or equivalent efficacy compared with unfractionated heparin?
J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1699 - 1712.
[Abstract] [Full Text] [PDF]


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BloodHome page
N. von Beckerath, W. Koch, J. Mehilli, C. Bottiger, A. Schomig, and A. Kastrati
Glycoprotein Ia gene C807T polymorphism and risk for major adverse cardiac events within the first 30 days after coronary artery stenting
Blood, June 1, 2000; 95(11): 3297 - 3301.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
P. Golino, M. Ragni, P. Cirillo, A. Scognamiglio, A. Ravera, C. Buono, A. Guarino, O. Piro, C. Lambiase, F. Botticella, et al.
Recombinant human, active site-blocked factor VIIa reduces infarct size and no-reflow phenomenon in rabbits
Am J Physiol Heart Circ Physiol, May 1, 2000; 278(5): H1507 - H1516.
[Abstract] [Full Text] [PDF]


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CirculationHome page
K. P. Rentrop
Thrombi in Acute Coronary Syndromes : Revisited and Revised
Circulation, April 4, 2000; 101(13): 1619 - 1626.
[Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
E. Arnaud, V. Barbalat, V. Nicaud, F. Cambien, A. Evans, C. Morrison, D. Arveiler, G. Luc, J.-B. Ruidavets, J. Emmerich, et al.
Polymorphisms in the 5' Regulatory Region of the Tissue Factor Gene and the Risk of Myocardial Infarction and Venous Thromboembolism : The ECTIM and PATHROS Studies
Arterioscler Thromb Vasc Biol, March 1, 2000; 20(3): 892 - 898.
[Abstract] [Full Text] [PDF]


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CirculationHome page
Z. Mallat, H. Benamer, B. Hugel, J. Benessiano, P. G. Steg, J.-M. Freyssinet, and A. Tedgui
Elevated Levels of Shed Membrane Microparticles With Procoagulant Potential in the Peripheral Circulating Blood of Patients With Acute Coronary Syndromes
Circulation, February 29, 2000; 101(8): 841 - 843.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
A. D. Schecter, T. M. Calderon, A. B. Berman, C. M. McManus, J. T. Fallon, M. Rossikhina, W. Zhao, G. Christ, J. W. Berman, and M. B. Taubman
Human Vascular Smooth Muscle Cells Possess Functional CCR5
J. Biol. Chem., February 25, 2000; 275(8): 5466 - 5471.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
E. Napoleone, A. Di Santo, M. Camera, E. Tremoli, and R. Lorenzet
Angiotensin-Converting Enzyme Inhibitors Downregulate Tissue Factor Synthesis in Monocytes
Circ. Res., February 4, 2000; 86(2): 139 - 143.
[Abstract] [Full Text] [PDF]


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CirculationHome page
M. K. Al-Obaidi, H. Philippou, P. J. Stubbs, A. Adami, R. Amersey, M. M. Noble, and D. A. Lane
Relationships Between Homocysteine, Factor VIIa, and Thrombin Generation in Acute Coronary Syndromes
Circulation, February 1, 2000; 101(4): 372 - 377.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
M. M Kockx and A. G Herman
Apoptosis in atherosclerosis: beneficial or detrimental?
Cardiovasc Res, February 1, 2000; 45(3): 736 - 746.
[Abstract] [Full Text] [PDF]


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CirculationHome page
P. Zoldhelyi, J. McNatt, H. S. Shelat, Y. Yamamoto, Z.-Q. Chen, and J. T. Willerson
Thromboresistance of Balloon-Injured Porcine Carotid Arteries After Local Gene Transfer of Human Tissue Factor Pathway Inhibitor
Circulation, January 25, 2000; 101(3): 289 - 295.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
C. J. Vaughan, A. M. Gotto Jr., and C. T. Basson
The evolving role of statins in the management of atherosclerosis
J. Am. Coll. Cardiol., January 1, 2000; 35(1): 1 - 10.
[Abstract] [Full Text] [PDF]


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CirculationHome page
E. M. Antman, C. H. McCabe, E. P. Gurfinkel, A. G. G. Turpie, P. J. L. M. Bernink, D. Salein, A. Bayes de Luna, K. Fox, J.-M. Lablanche, D. Radley, et al.
Enoxaparin Prevents Death and Cardiac Ischemic Events in Unstable Angina/Non-Q-Wave Myocardial Infarction : Results of the Thrombolysis In Myocardial Infarction (TIMI) 11B Trial
Circulation, October 12, 1999; 100(15): 1593 - 1601.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
H. Soejima, H. Ogawa, H. Yasue, K. Kaikita, K. Takazoe, K. Nishiyama, K. Misumi, S. Miyamoto, M. Yoshimura, K. Kugiyama, et al.
Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction
J. Am. Coll. Cardiol., October 1, 1999; 34(4): 983 - 988.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
R. C. Becker, F. A. Spencer, Y. Li, S. P. Ball, Y. Ma, T. Hurley, and J. Hebert
Thrombin generation after the abrupt cessation of intravenous unfractionated heparin among patients with acute coronary syndromes: Potential mechanisms for heightened prothrombotic potential
J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1020 - 1027.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
J. St. Pierre, L.-Y. Yang, K. Tamirisa, D. Scherrer, P. De Ciechi, P. Eisenberg, E. Tolunay, and D. Abendschein
Tissue Factor Pathway Inhibitor Attenuates Procoagulant Activity and Upregulation of Tissue Factor at the Site of Balloon-Induced Arterial Injury in Pigs
Arterioscler Thromb Vasc Biol, September 1, 1999; 19(9): 2263 - 2268.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
J.-P. Bossavy, K. S. Sakariassen, C. Thalamas, B. Boneu, and Y. Cadroy
Antithrombotic Efficacy of the Vitamin K Antagonist Fluindione in a Human Ex Vivo Model of Arterial Thrombosis : Effect of Anticoagulation Level and Combination Therapy With Aspirin
Arterioscler Thromb Vasc Biol, September 1, 1999; 19(9): 2269 - 2275.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
J. P. Bossavy, K. S. Sakariassen, K. Rubsamen, C. Thalamas, B. Boneu, and Y. Cadroy
Comparison of the Antithrombotic Effect of PEG-Hirudin and Heparin in a Human Ex Vivo Model of Arterial Thrombosis
Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1348 - 1353.
[Abstract] [Full Text] [PDF]