(Circulation. 1995;91:619-622.)
© 1995 American Heart Association, Inc.
Articles |
Differential Expression of Tissue Factor Protein in Directional Atherectomy Specimens From Patients With Stable and Unstable Coronary Syndromes
From the Division of Cardiology, Duke University and Durham VA Medical Centers, Durham, NC, and the Cardiovascular Biology Research Program (J.H.M.), Oklahoma Medical Research Foundation, Oklahoma City, Okla.
Correspondence to Brian H. Annex, MD, Duke University Medical Center, 508 Fulton St, Box 111A, Durham, NC 27705.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background Tissue factor (TF) is a cell membrane–associated protein that catalyzes the rate-limiting step of the extrinsic coagulation pathway, which is the major source of thrombin production in vivo. To explore the potential role that TF may play in ischemic coronary syndromes, directional coronary atherectomy specimens were tested for the presence of TF protein using immunohistochemical techniques.
Methods and Results Frozen sections from atherectomy specimens in 61 patients were examined for TF expression using an IgG murine monoclonal antibody against human TF. Patients were classified according to their admission diagnosis as having either an unstable or a stable coronary syndrome. An unstable coronary syndrome was defined as either angina pectoris occurring at rest or post–myocardial infarction (<1 week) angina. Stable coronary syndromes included patients with stable, progressive, and new-onset (<6 weeks) angina without rest pain. TF was detected in 15 (43%) of 35 patients with unstable coronary syndromes versus only 3 (12%) of 26 patients with stable coronary syndromes (odds ratio, 5.7; 95% confidence interval, 1.3 to 24.3; P=.018). Within the subgroup of patients with unstable coronary syndromes, TF was detected in 14 (60%) of 25 patients with de novo lesions versus only 1 (10%) of 10 patients with a restenosis lesion (P<.02). An additional 8 patients with stable coronary syndromes due to a restenosis lesion were also negative for TF. Therefore, the overall incidence of TF expression was only 6% (1 of 18) in restenosis lesions compared with 33% (14 of 43) in de novo lesions (P<.03).
Conclusions This study provides the first description of TF protein expression in human coronary artery lesions in vivo. Tissue factor was readily detected in de novo lesions in patients with unstable coronary syndromes, suggesting a role for TF in the pathogenesis of this disease process. Conversely, TF was rarely detected in patients with restenosis lesions even if the resulting clinical presentation was an unstable coronary syndrome. These results may have implications for the management of patients with unstable angina from de novo lesions and patients with ischemic symptoms from a restenosis lesion.
Key Words: angioplasty • thrombosis • angina • stenosis
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Tissue factor (TF) is a cell membrane–associated glycoprotein that serves as the primary initiator of the extrinsic coagulation cascade.1 TF binds to and acts as an essential cofactor for plasma protease factor VII, and the resulting complex activates factors IX and X, which leads to the major source of thrombin production in vivo.2 Therefore, TF is a critical protein in the activation of the coagulation cascade and may play an important role in the pathogenesis of ischemic coronary syndromes by mediating intravascular thrombosis.
Immunohistochemical analysis and in situ hybridization studies have demonstrated high levels of TF protein and mRNA in the adventitia of normal human blood vessels such as internal mammary arteries, aorta, and saphenous veins.3 4 Although TF protein is variably present in the media of some normal arteries, TF protein and mRNA are consistently undetectable in the intima and endothelium.3 4 Wilcox et al4 found that atherosclerotic plaques from human carotid endarterectomy specimens demonstrated islands of TF antigen staining surrounding cholesterol clefts and necrotic cores, while some foam cells, monocytes, and mesenchymal-like intimal cells in these plaques were positive for TF mRNA. Likewise, studies in several different cell types have shown that TF expression can be induced and upregulated by agents or physiological mediators that may play a role in atherosclerosis and arterial injury.5 6 7
At present, the frequency and the pattern of expression of TF in diseased human coronary arteries are unknown, and this information is necessary to begin to understand the role that TF may play in different coronary syndromes. The purpose of this study was therefore to determine the presence of TF expression in directional atherectomy specimens from patients undergoing revascularization for symptomatic coronary artery disease.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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The study included 61 patients who underwent directional coronary atherectomy at Duke University Medical Center between July 1991 and June 1992 or at Duke University and the Durham VA Medical Center between October 1993 and June 1994 from whom adequate tissue was available. In 50 patients, the atherectomy was performed as the initial percutaneous revascularization strategy and in 11 patients, it was performed as a "salvage" procedure immediately after an unsuccessful angioplasty (n=8) or threatened vessel closure (n=3). Patients with total coronary occlusions or unequivocal angiographic coronary thrombus before the intervention were not included in this study. Investigations were conducted under protocols approved by the institutional review boards of both institutions.
Pertinent information from patient histories and procedural outcomes was extracted from the Duke Databank for Cardiovascular Disease after the tissue analysis was complete. Patients were classified according to their admission diagnosis as having either an unstable or a stable coronary syndrome. An unstable coronary syndrome was defined as either angina pectoris occurring at rest or post–myocardial infarction (<1 week) angina. Stable coronary syndromes included patients with stable, progressive, and new-onset (<6 weeks) angina without rest pain. A restenosis lesion was defined when an atherectomy was performed (>1 week, <6 months) after an interventional procedure at the same site.
Atherectomy specimens were immediately removed from the cutter housing and immersed in ice-cold 4% paraformaldehyde (Fisher Scientific Co). After 2 to 4 hours, the samples were transferred to 30% sucrose–phosphate-buffered saline solution (PBS), embedded in OCT compound (Miles Scientific Division), snap-frozen in liquid nitrogen, and stored at -70°C. The samples were cryosectioned (6 µm) onto silane-coated microscope slides, which were quickly placed in cold acetone for 2 minutes and stored at -70°C. Samples of human skin were handled in a similar manner.
Immunohistochemistry was performed using a murine monoclonal antibody
against human tissue factor (TF9-9C3), as previously
described.3 Briefly, slides were thawed and dehydrated in
PBS. Blocking solution (10% horse serum) was applied for 30 minutes at
room temperature. The TF antibody was diluted to a concentration of 0.1
µg/mL in 10% horse serum and applied for 60 minutes at 37°C in a
humidified chamber. This was followed sequentially by incubation with
biotinylated anti-mouse IgG and ABC reagent according to
manufacturer's specifications (Vectastain ABC kit, Vector
Laboratories, Inc). Levamisole was added to block endogenous alkaline
phosphatase activity, and immune complexes were localized using the
chromogenic alkaline phosphatase substrate Vector Red (Vector
Laboratories, Inc). The sections were counterstained with hematoxylin,
dehydrated, and mounted with Permount (Fisher Scientific). Samples were
tested in duplicate on separate days. In all experiments, a sample of
human skin was included as a positive control, and the adjacent section
was handled in parallel with a nonsense murine IgG monoclonal antibody
as a negative control. Slides were reviewed independently by two
different observers (B.H.A., S.M.D.) without knowledge of the clinical
status. The results were expressed dichotomously as positive or
negative. Histological thrombus was identified by hematoxylin-eosin
stains, as previously described, and verified by trichrome
stains.8 For statistical analysis, the Fisher's exact
or 
2 test was used to compare the frequency of
expression of TF in the patient populations.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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The patients' demographic data are summarized in the Table
. The study included 35 patients who presented
with unstable coronary syndromes and 26 patients with stable coronary
syndromes. The group with stable coronary syndromes included new-onset
angina (n=2), progressive angina (n=17), and stable angina
(n=7). The
frequency of restenosis lesions was similar in both groups. The mean
time from the prior angioplasty for the entire restenosis group was
2.4±0.3 months (mean±SEM).
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Two representative lesions that demonstrated TF staining are
shown in Fig 1. Overall, TF was detected in 15 (43%) of
35 patients with unstable coronary syndromes versus only 3 (12%) of 26
patients with stable coronary syndromes (odds ratio, 5.7; 95%
confidence interval, 1.3 to 24.3; P=.018) (Fig
2, left). Within the subgroup of patients with unstable
coronary syndromes, TF was detected in 14 (60%) of 25 patients with a
de novo lesion versus only 1 (10%) of 10 patients with a restenosis
lesion (P<.02) (Fig 2, middle). An additional 8
patients
with stable coronary syndromes due to a restenosis lesion were also
negative for TF, for an overall incidence of only 6% (1 of 18) in
restenosis lesions compared with 33% (14 of 43) in de novo lesions
(P<.03) (Fig 2, right).
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Clinical and histological features that may have been related to TF
expression were examined. This study included some patients in whom
atherectomy was performed as a "salvage" procedure after balloon
angioplasty or as a procedure to treat a vein graft stenosis
(Table
).
The 11 salvage lesions included 6 patients with unstable coronary
syndromes and 5 with stable coronary syndromes. The incidence of TF
expression was 3 (27%) of 11, with two of the three positives found in
patients with an unstable coronary syndrome. The 7 vein graft lesions
included 5 patients with unstable and 2 with stable coronary syndromes.
The incidence of TF expression was 3 (43%) of 7, with two of the three
positives found in patients with unstable coronary syndromes. These
small groups appeared to be representative of the larger study
population and were included in the analysis. The time interval
from the onset of symptoms until atherectomy, for the unstable coronary
syndrome group, was similar for the TF-positive (5.3±1.0; range, 1 to
12 days) and TF-negative patients (4.9±0.9; range, 1 to 10 days).
Also, the frequency of histological thrombus was similar in the
TF-positive and TF-negative patients, 33% versus 37%,
respectively.
Four patients had an abrupt closure after the atherectomy procedure.
One occurred in the catheterization laboratory; one occurred 12 hours
after and two occurred 48 hours after the procedure. All lesions were
de novo native coronary arteries and were TF positive. Two patients had
stable and two had unstable coronary syndromes. Therefore, 4 (22%) of
the 18 patients with immunohistochemical staining for TF had an abrupt
closure. Although the number of events was small, the association of TF
expression with abrupt closure was highly significant
(P
.006).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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TF is the primary initiator of intravascular thrombosis and thrombin production in vivo.1 2 However, the precise role that TF plays in the pathogenesis of ischemic coronary syndromes is unknown. This study provides the first analysis of TF protein expression in human coronary artery lesions in vivo. The major findings of this study are that TF is frequently present in de novo lesions in patients with unstable coronary syndromes and that TF is rarely detected in restenosis lesions regardless of the patient's clinical presentation.
The frequent expression of TF in de novo lesions in patients with unstable coronary syndromes suggests that TF plays a central role in the pathogenesis of this disease process. These findings may be particularly important, with the emergence of several new potent antithrombotic agents.9 Our results suggest that patients with unstable coronary syndromes from de novo lesions may particularly benefit from the use of direct thrombin or TF pathway inhibitors. Conversely, although the absence of TF expression in restenosis lesions does not rule out TF as a potential cause of angioplasty restenosis, our results suggest that restenosis lesions have a low thrombotic potential regardless of the patient's clinical presentation. These findings may have implications for the potential use of adjunctive pharmacological therapies or interventional treatment strategies to treat restenosis lesions.
The results of this study also may provide evidence that mechanisms other than thrombus formation can be involved in the pathogenesis of unstable coronary syndromes. Angioscopic, angiographic, and pathological studies in patients with unstable angina have consistently identified a significant (20% to 50%) fraction of patients who lack evidence of plaque rupture or thrombus formation.10 11 12 A similar percentage of the patients in our study with unstable coronary syndromes and de novo lesions had no immunohistochemical TF protein expression. Flugelman et al13 studied directional coronary atherectomy specimens from de novo lesions in patients with unstable angina compared with a group with ischemic coronary symptoms from angioplasty restenosis lesions and concluded that smooth muscle cell proliferation may lead to plaque expansion and luminal narrowing, resulting in the clinical syndrome of unstable angina pectoris. Indeed, a variety of different mediators may be involved in the pathogenesis of unstable coronary syndromes.14 TF expression, however, may serve as a useful marker to differentiate mechanisms for unstable coronary syndromes.
Although the number of events in our study was small, all 4 patients who suffered an abrupt closure after directional atherectomy were TF positive. Likewise, animal models have suggested that TF may play a role in angioplasty complications. Pawashe et al15 found that antibodies to TF inhibited arterial thrombosis in a rabbit balloon injury model. Marmur et al7 demonstrated that balloon injury in a rat aorta induced a 10-fold increase in TF coagulant activity and an upregulation of mRNA in less than 2 hours. In our study, TF expression was similar in the primary atherectomy and "salvage" atherectomy groups. However, the time from initial balloon inflation to tissue removal, which was estimated to be 90 minutes from review of the catheterization report, may have been too early to detect an increase in the immunohistochemical protein expression.
Several limitations of this study must be considered. First, sampling error may occur in studies that use coronary atherectomy samples. It is unlikely, however, that sampling error can account for the magnitude of the differences noted in this study. Second, we tested for immunohistochemically detectable TF, and a procoagulant assay may be more sensitive.3 However, the enzyme assay has limitations, including the inability to localize the pattern of TF expression and an even greater potential than immunohistochemistry for sampling error if the specimens are divided. The lesions treated by directional atherectomy may be a skewed group because in general, they are in large vessels, have a proximal location, and lack angiographic thrombus. Caution is necessary before generalizing some of these findings to other coronary lesions.
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Acknowledgments |
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This study was supported in part by an Initial Career Development Grant from the Duke Heart Center (B.H.A.).
Received November 7, 1994; accepted December 11, 1994.
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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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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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A. Nakagomi, S. B. Freedman, and C. L. Geczy Interferon-{gamma} and Lipopolysaccharide Potentiate Monocyte Tissue Factor Induction by C-Reactive Protein : Relationship With Age, Sex, and Hormone Replacement Treatment Circulation, April 18, 2000; 101(15): 1785 - 1791. [Abstract] [Full Text] [PDF]
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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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 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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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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 J. A. Ambrose and G. Dangas Unstable Angina: Current Concepts of Pathogenesis and Treatment Arch Intern Med, January 10, 2000; 160(1): 25 - 37. [Abstract] [Full Text] [PDF]
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S Kojima, H Nonogi, Y Miyao, S Miyazaki, Y Goto, A Itoh, S Daikoku, T Matsumoto, I Morii, and C Yutani Is preinfarction angina related to the presence or absence of coronary plaque rupture? Heart, January 1, 2000; 83(1): 64 - 68. [Abstract] [Full Text] [PDF]
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 U. Schonbeck, F. Mach, G. K. Sukhova, M. Herman, P. Graber, M. R. Kehry, and P. Libby CD40 Ligation Induces Tissue Factor Expression in Human Vascular Smooth Muscle Cells Am. J. Pathol., January 1, 2000; 156(1): 7 - 14. [Abstract] [Full Text] [PDF]
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M.-Z. Cui, M. S. Penn, and G. M. Chisolm Native and Oxidized Low Density Lipoprotein Induction of Tissue Factor Gene Expression in Smooth Muscle Cells Is Mediated by Both Egr-1 and Sp1 J. Biol. Chem., November 12, 1999; 274(46): 32795 - 32802. [Abstract] [Full Text] [PDF]
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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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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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M. Aikawa, S. J. Voglic, S. Sugiyama, E. Rabkin, M. B. Taubman, J. T. Fallon, and P. Libby Dietary Lipid Lowering Reduces Tissue Factor Expression in Rabbit Atheroma Circulation, September 14, 1999; 100(11): 1215 - 1222. [Abstract] [Full Text] [PDF]
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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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E Arbustini, B Dal Bello, P Morbini, A P Burke, M Bocciarelli, G Specchia, and R Virmani Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction Heart, September 1, 1999; 82(3): 269 - 272. [Abstract] [Full Text] [PDF]
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H. Soejima, H. Ogawa, H. Yasue, K. Kaikita, K. Nishiyama, K. Misumi, K. Takazoe, Y. Miyao, M. Yoshimura, K. Kugiyama, et al. Heightened Tissue Factor Associated With Tissue Factor Pathway Inhibitor and Prognosis in Patients With Unstable Angina Circulation, June 8, 1999; 99(22): 2908 - 2913. [Abstract] [Full Text] [PDF]
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B. D. Duscha, W. E. Kraus, S. J. Keteyian, M. J. Sullivan, H. J. Green, F. H. Schachat, A. M. Pippen, C. A. Brawner, J. M. Blank, and B. H. Annex Capillary density of skeletal muscle: A contributing mechanism for exercise intolerance in class II-III chronic heart failure independent of other peripheral alterations J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1956 - 1963. [Abstract] [Full Text] [PDF]
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J Ge, F Chirillo, J Schwedtmann, G Görge, M Haude, D Baumgart, V Shah, C von Birgelen, S Sack, H Boudoulas, et al. Screening of ruptured plaques in patients with coronary artery disease by intravascular ultrasound Heart, June 1, 1999; 81(6): 621 - 627. [Abstract] [Full Text]
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J. J. Badimon, M. Lettino, V. Toschi, V. Fuster, M. Berrozpe, J. H. Chesebro, and L. Badimon Local Inhibition of Tissue Factor Reduces the Thrombogenicity of Disrupted Human Atherosclerotic Plaques : Effects of Tissue Factor Pathway Inhibitor on Plaque Thrombogenicity Under Flow Conditions Circulation, April 13, 1999; 99(14): 1780 - 1787. [Abstract] [Full Text] [PDF]
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M. S. Penn, C. V. Patel, M.-Z. Cui, P. E. DiCorleto, and G. M. Chisolm LDL Increases Inactive Tissue Factor on Vascular Smooth Muscle Cell Surfaces : Hydrogen Peroxide Activates Latent Cell Surface Tissue Factor Circulation, April 6, 1999; 99(13): 1753 - 1759. [Abstract] [Full Text] [PDF]
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Z. Mallat, B. Hugel, J. Ohan, G. Leseche, J.-M. Freyssinet, and A. Tedgui Shed Membrane Microparticles With Procoagulant Potential in Human Atherosclerotic Plaques : A Role for Apoptosis in Plaque Thrombogenicity Circulation, January 26, 1999; 99(3): 348 - 353. [Abstract] [Full Text] [PDF]
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B. Engelmann, S. Zieseniss, K. Brand, S. Page, A. Lentschat, A. J. Ulmer, and E. Gerlach Tissue Factor Expression of Human Monocytes Is Suppressed by Lysophosphatidylcholine Arterioscler Thromb Vasc Biol, January 1, 1999; 19(1): 47 - 53. [Abstract] [Full Text] [PDF]
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D. Corseaux, T. Le Tourneau, I. Six, M. D. Ezekowitz, E. P. Mc Fadden, T. Meurice, P. Asseman, C. Bauters, and B. Jude Enhanced Monocyte Tissue Factor Response After Experimental Balloon Angioplasty in Hypercholesterolemic Rabbit: Inhibition With Dietary L-Arginine Circulation, October 27, 1998; 98(17): 1776 - 1782. [Abstract] [Full Text] [PDF]
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J M Mann, J C Kaski, W I Pereira, S Arie, J A Ramires, and F Pileggi Histological patterns of atherosclerotic plaques in unstable angina patients vary according to clinical presentation Heart, July 1, 1998; 80(1): 19 - 22. [Abstract] [Full Text]
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Z. S. Galis, K. Asanuma, D. Godin, and X. Meng N-Acetyl-Cysteine Decreases the Matrix-Degrading Capacity of Macrophage-Derived Foam Cells : New Target for Antioxidant Therapy? Circulation, June 23, 1998; 97(24): 2445 - 2453. [Abstract] [Full Text] [PDF]
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B. H. Annex, C. E. Torgan, P. Lin, D. A. Taylor, M. A. Thompson, K. G. Peters, and W. E. Kraus Induction and maintenance of increased VEGF protein by chronic motor nerve stimulation in skeletal muscle Am J Physiol Heart Circ Physiol, March 1, 1998; 274(3): H860 - H867. [Abstract] [Full Text] [PDF]
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P. Golino, M. Ragni, P. Cirillo, D. D'Andrea, A. Scognamiglio, A. Ravera, C. Buono, M. Ezban, N. Corcione, F. Vigorito, et al. Antithrombotic Effects of Recombinant Human, Active Site–Blocked Factor VIIa in a Rabbit Model of Recurrent Arterial Thrombosis Circ. Res., January 23, 1998; 82(1): 39 - 46. [Abstract] [Full Text] [PDF]
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A. D. Schecter, B. J. Rollins, Y. J. Zhang, I. F. Charo, J. T. Fallon, M. Rossikhina, P. L. A. Giesen, Y. Nemerson, and M. B. Taubman Tissue Factor Is Induced by Monocyte Chemoattractant Protein-1 in Human Aortic Smooth Muscle and THP-1 Cells J. Biol. Chem., November 7, 1997; 272(45): 28568 - 28573. [Abstract] [Full Text] [PDF]
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K. Kaikita, H. Ogawa, H. Yasue, M. Takeya, K. Takahashi, T. Saito, K. Hayasaki, K. Horiuchi, A. Takizawa, Y. Kamikubo, et al. Tissue Factor Expression on Macrophages in Coronary Plaques in Patients with Unstable Angina Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 2232 - 2237. [Abstract] [Full Text]
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F. Mach, U. Schonbeck, J.-Y. Bonnefoy, J. S. Pober, and P. Libby Activation of Monocyte/Macrophage Functions Related to Acute Atheroma Complication by Ligation of CD40 : Induction of Collagenase, Stromelysin, and Tissue Factor Circulation, July 15, 1997; 96(2): 396 - 399. [Abstract] [Full Text]
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K. M. Channon, G. J. Fulton, M. G. Davies, K. G. Peters, M. D. Ezekowitz, P.-O. Hagen, and B. H. Annex Modulation of Tissue Factor Protein Expression in Experimental Venous Bypass Grafts Arterioscler Thromb Vasc Biol, July 1, 1997; 17(7): 1313 - 1319. [Abstract] [Full Text]
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V. Toschi, R. Gallo, M. Lettino, J. T. Fallon, S. D. Gertz, A. Fernandez-Ortiz, J. H. Chesebro, L. Badimon, Y. Nemerson, V. Fuster, et al. Tissue Factor Modulates the Thrombogenicity of Human Atherosclerotic Plaques Circulation, February 4, 1997; 95(3): 594 - 599. [Abstract] [Full Text]
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P. R. Moreno, V. H. Bernardi, J. Lopez-Cuellar, A. M. Murcia, I. F. Palacios, H. K. Gold, R. Mehran, S. K. Sharma, Y. Nemerson, V. Fuster, et al. Macrophages, Smooth Muscle Cells, and Tissue Factor in Unstable Angina: Implications for Cell-Mediated Thrombogenicity in Acute Coronary Syndromes Circulation, December 15, 1996; 94(12): 3090 - 3097. [Abstract] [Full Text]
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M. J. Davies Stability and Instability: Two Faces of Coronary Atherosclerosis: The Paul Dudley White Lecture 1995 Circulation, October 15, 1996; 94(8): 2013 - 2020. [Full Text]
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J. D. Marmur, S. V. Thiruvikraman, B. S. Fyfe, A. Guha, S. K. Sharma, J. A. Ambrose, J. T. Fallon, Y. Nemerson, and M. B. Taubman Identification of Active Tissue Factor in Human Coronary Atheroma Circulation, September 15, 1996; 94(6): 1226 - 1232. [Abstract] [Full Text]
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J. T. Willerson Inhibitors of Platelet Glycoprotein IIb/IIIa Receptors: Will They Be Useful When Given Chronically? Circulation, September 1, 1996; 94(5): 866 - 868. [Full Text]
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J. A. Ambrose and M. Weinrauch Thrombosis in Ischemic Heart Disease Arch Intern Med, July 8, 1996; 156(13): 1382 - 1394. [Abstract] [PDF]
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S. Waxman, M. A. Sassower, M. A. Mittleman, S. Zarich, A. Miyamoto, K. S. Manzo, J. E. Muller, G. S. Abela, and R. W. Nesto Angioscopic Predictors of Early Adverse Outcome After Coronary Angioplasty in Patients With Unstable Angina and Non–Q-Wave Myocardial Infarction Circulation, June 15, 1996; 93(12): 2106 - 2113. [Abstract] [Full Text]
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M. Ragni, P. Cirillo, I. Pascucci, A. Scognamiglio, D. D'Andrea, N. Eramo, M. D. Ezekowitz, A. B. Pawashe, M. Chiariello, and P. Golino Monoclonal Antibody Against Tissue Factor Shortens Tissue Plasminogen Activator Lysis Time and Prevents Reocclusion in a Rabbit Model of Carotid Artery Thrombosis Circulation, May 15, 1996; 93(10): 1913 - 1918. [Abstract] [Full Text]
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A. Farb, A. P. Burke, A. L. Tang, Y. Liang, P. Mannan, J. Smialek, and R. Virmani Coronary Plaque Erosion Without Rupture Into a Lipid Core : A Frequent Cause of Coronary Thrombosis in Sudden Coronary Death Circulation, April 1, 1996; 93(7): 1354 - 1363. [Abstract] [Full Text]
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Y. Jang, L. A. Guzman, A. M. Lincoff, M. Gottsauner-Wolf, F. Forudi, C. E. Hart, D. W. Courtman, M. Ezban, S. G. Ellis, and E. J. Topol Influence of Blockade at Specific Levels of the Coagulation Cascade on Restenosis in a Rabbit Atherosclerotic Femoral Artery Injury Model Circulation, November 15, 1995; 92(10): 3041 - 3050. [Abstract] [Full Text]
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E. Falk, P. K. Shah, and V. Fuster Coronary Plaque Disruption Circulation, August 1, 1995; 92(3): 657 - 671. [Full Text]
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P. Theroux Angiographic and Clinical Progression in Unstable Angina : From Clinical Observations to Clinical Trials Circulation, May 1, 1995; 91(9): 2295 - 2298. [Full Text]
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R. Singh, S. Pan, C. S. Mueske, T. Witt, L. S. Kleppe, T. E. Peterson, A. Slobodova, J.-Y. Chang, N. M. Caplice, and R. D. Simari Role for Tissue Factor Pathway in Murine Model of Vascular Remodeling Circ. Res., July 6, 2001; 89(1): 71 - 76. [Abstract] [Full Text] [PDF]
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