(Circulation. 1997;95:594-599.)
© 1997 American Heart Association, Inc.
Articles |
Tissue Factor Modulates the Thrombogenicity of Human Atherosclerotic Plaques
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
This article has been cited by other articles:
 |
|
 |
|
  L. G. Spagnoli, E. Bonanno, G. Sangiorgi, and A. Mauriello Role of Inflammation in Atherosclerosis J. Nucl. Med., November 1, 2007; 48(11): 1800 - 1815. [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]
|
|
|
|
 |
|
 E. Calvo, F. Tokumasu, O. Marinotti, J.-L. Villeval, J. M. C. Ribeiro, and I. M. B. Francischetti Aegyptin, a Novel Mosquito Salivary Gland Protein, Specifically Binds to Collagen and Prevents Its Interaction with Platelet Glycoprotein VI, Integrin {alpha}2beta1, and von Willebrand Factor J. Biol. Chem., September 14, 2007; 282(37): 26928 - 26938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gross, P. Tilly, D. Hentsch, J.-L. Vonesch, and J.-E. Fabre Vascular wall-produced prostaglandin E2 exacerbates arterial thrombosis and atherothrombosis through platelet EP3 receptors J. Exp. Med., February 19, 2007; 204(2): 311 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Camino-Lopez, V. Llorente-Cortes, J. Sendra, and L. Badimon Tissue factor induction by aggregated LDL depends on LDL receptor-related protein expression (LRP1) and Rho A translocation in human vascular smooth muscle cells Cardiovasc Res, January 1, 2007; 73(1): 208 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Terrier, A.-M. Piette, D. Kerob, F. Cordoliani, E. Tancrede, L. Hamidou, C. Lebbe, O. Bletry, and J.-E. Kahn Superficial Venous Thrombophlebitis as the Initial Manifestation of Hypereosinophilic Syndrome: Study of the First 3 Cases Arch Dermatol, December 1, 2006; 142(12): 1606 - 1610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Morel, F. Toti, B. Hugel, B. Bakouboula, L. Camoin-Jau, F. Dignat-George, and J.-M. Freyssinet Procoagulant Microparticles: Disrupting the Vascular Homeostasis Equation? Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2594 - 2604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Raupach, K. Schafer, S. Konstantinides, and S. Andreas Secondhand smoke as an acute threat for the cardiovascular system: a change in paradigm Eur. Heart J., February 2, 2006; 27(4): 386 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Tabas Consequences and Therapeutic Implications of Macrophage Apoptosis in Atherosclerosis: The Importance of Lesion Stage and Phagocytic Efficiency Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2255 - 2264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Jayachandran, A. Sanzo, W. G. Owen, and V. M. Miller Estrogenic regulation of tissue factor and tissue factor pathway inhibitor in platelets Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1908 - H1916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fuster, P. R. Moreno, Z. A. Fayad, R. Corti, and J. J. Badimon Atherothrombosis and High-Risk Plaque: Part I: Evolving Concepts J. Am. Coll. Cardiol., September 20, 2005; 46(6): 937 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Daugherty, N. R. Webb, D. L. Rateri, and V. L. King Thematic review series: The Immune System and Atherogenesis. Cytokine regulation of macrophage functions in atherogenesis J. Lipid Res., September 1, 2005; 46(9): 1812 - 1822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Libby and P. Theroux Pathophysiology of Coronary Artery Disease Circulation, June 28, 2005; 111(25): 3481 - 3488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Penz, A. J. Reininger, R. Brandl, P. Goyal, T. Rabie, I. Bernlochner, E. Rother, C. Goetz, B. Engelmann, P. A. Smethurst, et al. Human atheromatous plaques stimulate thrombus formation by activating platelet glycoprotein VI FASEB J, June 1, 2005; 19(8): 898 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Benagiano, M. M. D'Elios, A. Amedei, A. Azzurri, R. van der Zee, A. Ciervo, G. Rombola, S. Romagnani, A. Cassone, and G. Del Prete Human 60-kDa Heat Shock Protein Is a Target Autoantigen of T Cells Derived from Atherosclerotic Plaques J. Immunol., May 15, 2005; 174(10): 6509 - 6517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Morrow, S. A. Murphy, C. H. McCabe, N. Mackman, H. C. Wong, E. M. Antman, and on behalf of the PROXIMATE-TIMI 27 Investigators Potent inhibition of thrombin with a monoclonal antibody against tissue factor (Sunol-cH36): results of the PROXIMATE-TIMI 27 trial Eur. Heart J., April 1, 2005; 26(7): 682 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Llorente-Cortes and L. Badimon LDL Receptor-Related Protein and the Vascular Wall: Implications for Atherothrombosis Arterioscler. Thromb. Vasc. Biol., March 1, 2005; 25(3): 497 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Day, J. L. Reeve, B. Pedersen, D. M Farris, D. D. Myers, M. Im, T. W. Wakefield, N. Mackman, and W. P. Fay Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall Blood, January 1, 2005; 105(1): 192 - 198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fiorucci, A. Mencarelli, A. Meneguzzi, A. Lechi, B. Renga, P. del Soldato, A. Morelli, and P. Minuz Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans J. Am. Coll. Cardiol., August 4, 2004; 44(3): 635 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Llorente-Cortes, M. Otero-Vinas, S. Camino-Lopez, O. Llampayas, and L. Badimon Aggregated Low-Density Lipoprotein Uptake Induces Membrane Tissue Factor Procoagulant Activity and Microparticle Release in Human Vascular Smooth Muscle Cells Circulation, July 27, 2004; 110(4): 452 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F Viles-Gonzalez, V. Fuster, and J. J Badimon Atherothrombosis: A widespread disease with unpredictable and life-threatening consequences Eur. Heart J., July 2, 2004; 25(14): 1197 - 1207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Priebe Triggers of perioperative myocardial ischaemia and infarction Br. J. Anaesth., July 1, 2004; 93(1): 9 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hutter, C. Valdiviezo, B. V. Sauter, M. Savontaus, I. Chereshnev, F. E. Carrick, G. Bauriedel, B. Luderitz, J. T. Fallon, V. Fuster, et al. Caspase-3 and Tissue Factor Expression in Lipid-Rich Plaque Macrophages: Evidence for Apoptosis as Link Between Inflammation and Atherothrombosis Circulation, April 27, 2004; 109(16): 2001 - 2008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Viswambharan, X.-F. Ming, S. Zhu, A. Hubsch, P. Lerch, G. Vergeres, S. Rusconi, and Z. Yang Reconstituted High-Density Lipoprotein Inhibits Thrombin-Induced Endothelial Tissue Factor Expression Through Inhibition of RhoA and Stimulation of Phosphatidylinositol 3-Kinase but not Akt/Endothelial Nitric Oxide Synthase Circ. Res., April 16, 2004; 94(7): 918 - 925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Lev, D. Hasdai, E. Scapa, A. Tobar, A. Assali, J. Lahav, A. Battler, J. J. Badimon, and R. Kornowski Administration of eptifibatide to acute coronary syndrome patients receiving enoxaparin or unfractionated heparin: Effect on platelet function and thrombus formation J. Am. Coll. Cardiol., March 17, 2004; 43(6): 966 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Golino, A. Ravera, M. Ragni, P. Cirillo, O. Piro, and M. Chiariello Involvement of Tissue Factor Pathway Inhibitor in the Coronary Circulation of Patients With Acute Coronary Syndromes Circulation, December 9, 2003; 108(23): 2864 - 2869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Bea, E. Blessing, B. J Bennett, C. C. Kuo, L. A. Campbell, J. Kreuzer, and M. E Rosenfeld Chronic inhibition of cyclooxygenase-2 does not alter plaque composition in a mouse model of advanced unstable atherosclerosis Cardiovasc Res, October 15, 2003; 60(1): 198 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Pierre-Paul and V. Gahtan Noncholesterol-Lowering Effects of Statins Vascular and Endovascular Surgery, September 1, 2003; 37(5): 301 - 313. [Abstract] [PDF]
|
|
|
|
|
|
M. Camera, M. Frigerio, V. Toschi, M. Brambilla, F. Rossi, D. C. Cottell, P. Maderna, A. Parolari, R. Bonzi, O. De Vincenti, et al. Platelet Activation Induces Cell-Surface Immunoreactive Tissue Factor Expression, Which Is Modulated Differently by Antiplatelet Drugs Arterioscler. Thromb. Vasc. Biol., September 1, 2003; 23(9): 1690 - 1696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D'Andrea, M. Ravera, P. Golino, A. Rosica, M. De Felice, M. Ragni, P. Cirillo, F. Vigorito, N. Corcione, P. Tommasini, et al. Induction of Tissue Factor in the Arterial Wall During Recurrent Thrombus Formation Arterioscler. Thromb. Vasc. Biol., September 1, 2003; 23(9): 1684 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Bijsterveld, A. H. Moons, J. C. M. Meijers, M. Levi, H. R. Buller, and R. J. G. Peters The impact on coagulation of an intravenous loading dose in addition to a subcutaneousregimen of low-molecular-weight heparinin the initial treatment of acute coronary syndromes J. Am. Coll. Cardiol., August 6, 2003; 42(3): 424 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. M. Moons, R. J. G. Peters, N. R. Bijsterveld, J. J. Piek, M. H. Prins, G. P. Vlasuk, W. E. Rote, and H. R. Buller Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplastyAppendix J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2147 - 2153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yamashita, Y. Asada, H. Sugimura, H. Yamamoto, K. Marutsuka, K. Hatakeyama, S. Tamura, Y. Ikeda, and A. Sumiyoshi Contribution of von Willebrand Factor to Thrombus Formation on Neointima of Rabbit Stenotic Iliac Artery Under High Blood-Flow Velocity Arterioscler. Thromb. Vasc. Biol., June 1, 2003; 23(6): 1105 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Benagiano, A. Azzurri, A. Ciervo, A. Amedei, C. Tamburini, M. Ferrari, J. L. Telford, C. T. Baldari, S. Romagnani, A. Cassone, et al. T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions PNAS, May 27, 2003; 100(11): 6658 - 6663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jneid, D. L. Bhatt, R. Corti, J. J. Badimon, V. Fuster, and G. S. Francis Aspirin and Clopidogrel in Acute Coronary Syndromes: Therapeutic Insights From the CURE Study Arch Intern Med, May 26, 2003; 163(10): 1145 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Watson, A. K. C. Chan, L. R. Berry, J. Li, S. K. Sood, J. G. Dickhout, L. Xu, G. H. Werstuck, L. Bajzar, H. J. Klamut, et al. Overexpression of the 78-kDa Glucose-regulated Protein/Immunoglobulin-binding Protein (GRP78/BiP) Inhibits Tissue Factor Procoagulant Activity J. Biol. Chem., May 2, 2003; 278(19): 17438 - 17447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. S. Nesbitt, S. Giuliano, S. Kulkarni, S. M. Dopheide, I. S. Harper, and S. P. Jackson Intercellular calcium communication regulates platelet aggregation and thrombus growth J. Cell Biol., March 31, 2003; 160(7): 1151 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sambola, J. Osende, J. Hathcock, M. Degen, Y. Nemerson, V. Fuster, J. Crandall, and J. J. Badimon Role of Risk Factors in the Modulation of Tissue Factor Activity and Blood Thrombogenicity Circulation, February 25, 2003; 107(7): 973 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Corti, V. Fuster, and J. J. Badimon Pathogenetic concepts of acute coronary syndromes J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 7S - 14S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Shah Mechanisms of plaque vulnerability and rupture J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 15S - 22S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-Z. Cui, G. Zhao, A. L. Winokur, E. Laag, J. R. Bydash, M. S. Penn, G. M. Chisolm, and X. Xu Lysophosphatidic Acid Induction of Tissue Factor Expression in Aortic Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 224 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Morishige, H. Shimokawa, Y. Matsumoto, Y. Eto, T. Uwatoku, K. Abe, K. Sueishi, and A. Takeshita Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo Cardiovasc Res, February 1, 2003; 57(2): 572 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fiorucci, A. Mencarelli, A. Meneguzzi, A. Lechi, A. Morelli, P. del Soldato, and P. Minuz NCX-4016 (NO-Aspirin) Inhibits Lipopolysaccharide-Induced Tissue Factor Expression In Vivo: Role of Nitric Oxide Circulation, December 10, 2002; 106(24): 3120 - 3125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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 in patients presenting without persistent ST-segment elevation Eur. Heart J., December 1, 2002; 23(23): 1809 - 1840. [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Forrester Prevention of Plaque Rupture: A New Paradigm of Therapy Ann Intern Med, November 19, 2002; 137(10): 823 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kluft, R. Kleemann, and M.P.M. de Maat How best to counteract the enemies? By controlling inflammation in the coronary circulation Eur. Heart J. Suppl., November 1, 2002; 4(suppl_G): G53 - G65. [Abstract] [PDF]
|
|
|
|
|
|
F. A. Jaffer, C.-H. Tung, R. E. Gerszten, and R. Weissleder In Vivo Imaging of Thrombin Activity in Experimental Thrombi With Thrombin-Sensitive Near-Infrared Molecular Probe Arterioscler. Thromb. Vasc. Biol., November 1, 2002; 22(11): 1929 - 1935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-i. Kotani, S. Nanto, G. S. Mintz, M. Kitakaze, T. Ohara, T. Morozumi, S. Nagata, and M. Hori Plaque Gruel of Atheromatous Coronary Lesion May Contribute to the No-Reflow Phenomenon in Patients With Acute Coronary Syndrome Circulation, September 24, 2002; 106(13): 1672 - 1677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Cadroy, F. Pillard, K. S. Sakariassen, C. Thalamas, B. Boneu, and D. Riviere Strenuous but not moderate exercise increases the thrombotic tendency in healthy sedentary male volunteers J Appl Physiol, September 1, 2002; 93(3): 829 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Lev, J. D. Marmur, M. Zdravkovic, J. I. Osende, J. Robbins, J. A. Delfin, M. Richard, E. Erhardtsen, M. S. Thomsen, A. M. Lincoff, et al. Antithrombotic Effect of Tissue Factor Inhibition by Inactivated Factor VIIa: An Ex Vivo Human Study Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 1036 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Ananyeva, D. V. Kouiavskaia, M. Shima, and E. L. Saenko Intrinsic pathway of blood coagulation contributes to thrombogenicity of atherosclerotic plaque Blood, May 29, 2002; 99(12): 4475 - 4485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Baetta, M. Camera, C. Comparato, C. Altana, M. D. Ezekowitz, and E. Tremoli Fluvastatin Reduces Tissue Factor Expression and Macrophage Accumulation in Carotid Lesions of Cholesterol-Fed Rabbits in the Absence of Lipid Lowering Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 692 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H.M Moons, M. Levi, and R. J.G Peters Tissue factor and coronary artery disease Cardiovasc Res, February 1, 2002; 53(2): 313 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Shah Reduced Tissue Factor Pathway Inhibitor-1 After Pharmacological Thrombolysis: An Epiphenomenon or Potential Culprit in Rethrombosis? Circulation, January 22, 2002; 105(3): 270 - 271. [Full Text] [PDF]
|
|
|
|
|
|
D. Ardissino, P. A. Merlini, K. A. Bauer, E. Bramucci, M. Ferrario, R. Coppola, R. Fetiveau, S. Lucreziotti, R. D. Rosenberg, and P. M. Mannucci Thrombogenic potential of human coronary atherosclerotic plaques Blood, November 1, 2001; 98(9): 2726 - 2729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. A. Fayad and V. Fuster Clinical Imaging of the High-Risk or Vulnerable Atherosclerotic Plaque Circ. Res., August 17, 2001; 89(4): 305 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Golino, P. Cirillo, P. Calabro', M. Ragni, D. D'Andrea, E. V. Avvedimento, F. Vigorito, N. Corcione, F. Lo |