(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.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
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
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Thrombus formation on a disrupted atherosclerotic lesion plays a fundamental role in the development of acute coronary syndromes and the progression of atherosclerosis.1 2 Angiography, angioscopy, and necropsy studies have shown thrombi on ulcerated or fissured atherosclerotic plaques in patients with myocardial infarction, unstable angina, and sudden cardiac death.3 4 5 6 7 8 The thrombogenicity of atherosclerotic lesions is determined by the nature and extent of the plaque component exposed to flowing blood together with local rheological and systemic blood factors. We9 have recently demonstrated that platelet deposition and thrombus formation on the lipid-rich atheromatous core exposed to flowing blood is up to sixfold greater than that on other substrates, including collagen-rich matrix.
TF is a small-molecular-weight glycoprotein that initiates the extrinsic clotting cascade and is considered a major regulator of coagulation, hemostasis, and thrombosis. TF forms a high-affinity complex with coagulation factors VII and VIIa; TF-VIIa complex activates factors IX and X, which in turn leads to thrombin generation.10 11
TF antigen has been demonstrated in endarterectomy specimens from patients with carotid atherosclerosis12 and, more recently, in some atherectomy specimens from culprit lesions in patients with unstable coronary syndromes.13 This suggests a potential role for this protein in the thrombotic complication of atherosclerosis after plaque disruption. Our group has developed a novel approach for the in situ identification of TF by using Dig-FVIIa.14
The present study correlates platelet deposition on human atherosclerotic plaques and normal vessel components exposed to flowing blood with the content of TF on the surface of the exposed arterial substrate. The aim of this study was to clarify the causative role of TF in the thrombogenicity of disrupted atherosclerotic plaques.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Preparation of Human Arterial Specimens and Classification
Different types of human atherosclerotic plaques and normal arterial segments were obtained from human aortas at autopsy within 24 hours of death. Lesions were selected according to the following macroscopic criteria: (1) fatty streaks, characterized by slightly raised yellow dots or streaks; (2) fibrous plaques, characterized by raised, pearly white lesions without a soft core; and (3) atheromatous lipid-rich core, characterized by raised white or yellow-white plaques containing a soft yellow core of toothpastelike consistency, separated from the lumen by a fibrous cap. Macroscopically normal aortic segments were also selected. Specimens were cut into segments (2.8x0.8 cm) and kept frozen at -70°C.
To mimic the in vivo situation of plaque disruption and to directly expose the internal components of the atherosclerotic plaque, the superficial layers of the plaque were removed as previously described.9 In all instances, the exposed substrates were part of the intimal layer of the diseased vessel (above the internal elastic lamina). Special care was taken to avoid gross irregularities on the surface. Normal tunica media was prepared by peeling off the intimal layer with a thin portion of subjacent media starting from a corner of the aortic segment, as previously described.9
Perfusion Chamber
The acrylic perfusion chamber used in the present study has been described elsewhere.15 16 The arterial segment to be tested was placed in the chamber with a portion of the wall (25 mm in length) replacing a part of the tubular flow channel (1 mm in diameter), permitting the surface of each specimen to be directly exposed to the flowing blood. Human atherosclerotic plaques were exposed to flowing blood at a flow rate of 10 mL/min for 5-minute perfusion periods. This experimental flow condition in this laminar perfusion system gives a theoretically calculated local shear rate of 1690/s (Reynolds number, 60; average blood velocity, 21.2 cm/s) and corresponds to the local rheological conditions that develop in a mild to moderately stenotic coronary artery. Our previous work15 demonstrated that these rheological conditions result in consistent levels of platelet deposition.
Experimental Procedure
Yorkshire albino pigs (body weight, 30±2 kg) were used as blood donors. All procedures were performed in accordance with the Mount Sinai School of Medicine and American Heart Association guidelines on research animal use. Pigs were initially sedated with ketamine (20 mg/kg body weight) followed by sodium pentobarbital (25 mg/kg IV). Anesthesia was maintained by infusion of pentobarbital as needed. An ex vivo extracorporeal perfusion system was set up as previously described.15 16 In brief, the catheterized carotid artery was connected by polyethylene tubing to the input of the acrylic chamber. The output of the chamber was connected to a peristaltic pump with interchangeable heads calibrated to maintain the selected blood flow (Masterflex model 7013). Blood that passed through the chamber was recirculated back into the animal by the external jugular vein. After carotid cannulation, baseline blood samples were taken for hematocrit, red blood cells, platelet count, fibrinogen levels, and aPTT measurement. The animals then received standard heparin (50 IU/kg bolus followed by continuous infusion of 50 IU/kg per hour). This regimen of administration achieved an aPTT ratio of 1.5±0.03x the baseline values (mean±SE). The specimens were mounted in the chamber and initially perfused with PBS (0.01 mol/L, pH 7.4, 37°C) for 60 seconds. Blood was subsequently perfused through the chamber at 10 mL/min for 5 minutes. At the end of the blood perfusions, PBS was again passed through the chamber for 30 seconds to wash away unattached cells and plasma proteins. All the perfusions were performed at 37°C by placing the chamber in a water bath. Hematocrit, platelet count, and fibrinogen levels were constant throughout each perfusion and were similar in all perfusions.
Radioactive Labeling of Platelets
Autologous platelets were labeled with 111In-tropolone in plasma and reinjected 16 to 24 hours before the perfusion experiments, as previously described.15 16 17 Labeling efficiency was 65±4%. The mean injected activity was 254.3±19.6 µCi with 2.8x106±0.4x106 reinjected indium-labeled platelets/µL in a total of 4 mL autologous platelet-poor plasma.
Measurement of Platelet Deposition
At the end of each perfusion, the arterial segments were removed and fixed overnight in 4% paraformaldehyde in 0.1 mol/L PBS, pH 7.4. Segments were individually counted in a 
-well counter (Packard Auto-Gamma 5650). The number of platelets deposited on each specimen was calculated by blood activity (counts) and platelet counts in blood and normalized to surface area. Values are expressed as number of platelets/cm2.15 16 17
Histological Evaluation
All specimens were routinely processed for paraffin embedding, with sectioning performed parallel to the direction of the flow. Exposed segments were step sectioned every 100 µm, and 5-µm sections were placed onto lysine-coated slides. Sections were deparaffinized, rehydrated, and stained with hematoxylin-eosin and trichrome techniques. Histological evaluation verified the initial macroscopic classification of lesion type.9 The gross classification of the specimens performed before blood perfusion was later confirmed by microscopic examination of the specimens.
In Situ Dig-FVIIa Binding
The presence of TF in the perfused human atherosclerotic and normal arterial segments was assessed by a newly developed in situ binding assay based on the high affinity between TF and factor VIIa. The assay involves the use of Dig-FVIIa.14 Positive digoxigenin staining indicates the existence of TF:FVIIa complex, the catalytic complex for activation of factor X. In brief, rehydrated sections were placed in TBS containing 5 mmol/L Ca2+ (pH 7.5). Sections were then incubated with 50 nmol/L Dig-FVIIa in TBS containing 5 mmol/L Ca2+ at 37°C for 2 hours. Sections were washed with TBS and fixed with 4% paraformaldehyde in TBS for 5 minutes. Sections were rinsed in TBS and incubated with a 1:1000 dilution of sheep Fab anti-digoxigenin conjugated with horseradish peroxidase at 37°C for 1 hour. Sections were again washed with TBS and reacted with 3,3'-diaminobenzidine (digoxigenin-3-0-methylcarbonyl-
-aminocaproic; Biogenex) for 10 minutes. Slides were washed in distilled water and dehydrated, coverslips were put on, and the slides were observed microscopically.
Dig-FVIIa staining controls were performed on selected specimens. Negative controls included replacement of Dig-FVIIa with unlabeled factor VIIa, staining with Dig-FVIIa in the presence of a 10-fold excess of unlabeled factor VIIa, and preincubation of sections with a polyclonal antibody to TF before Dig-FVIIa staining (see Fig 1
).
|
The TF content of each specimen beneath the thrombus was semiquantified by assigning an AU score of 0 (no staining) through 3 (the most staining) to each of the Dig-FVIIa–stained sections without knowledge of the quantitative platelet deposition data. The TF score for each specimen was determined by three different investigators, and their scores were averaged.
Hematologic Parameters
Number of blood cells, hematocrit, platelet number, and platelet size distribution were determined with the use of a system 9018 Serono cell analyzer equipped with a veterinarian software program to allow blood cell counting of different animal species. Monitoring of the aPTTs and plasma fibrinogen levels was determined with the use of an ST4 automated clotter and the corresponding specific kits (America Diagnostica) according to the manufacturer's instructions.
Statistical Analysis
All statistical analyses were performed with the use of Statview II software (Abacus Concept, Inc) on a Macintosh 7100/66AV microcomputer. Results are expressed as mean±SE unless otherwise stated. A value of P<.05 was considered significant. Between-group analyses were performed by one-factor ANOVA followed by Fisher's protected least-squares difference and Scheffe's F test to assess specific group differences.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Histological Analysis of Atherosclerotic Lesions
A total of 50 human arterial segments were analyzed. Histological evaluation confirmed the initial macroscopic classification of the lesions. Twenty-four were atherosclerotic plaques: 5 foam cell–rich, 9 collagen-rich, and 10 atheromatous lipid-rich core lesions. The remaining 26 arterial segments were normal (nonatherosclerotic) arterial components: 15 intimal, 5 medial, and 6 adventitial layers.
Platelet Thrombus Formation on the Different Types of Human Atherosclerotic Plaques
The results of thrombus formation on the different substrates exposed to flowing blood are shown in Fig 2. Thrombus formation on atheromatous core was significantly higher (712±213x106 platelets/cm2) than on all other substrates (adventitia, 203±58 platelets/cm2; tunica media, 134±41; foam cell–rich matrix, 97±46; collagen matrix, 96±16; and normal intima, 79±16x106; P=.0002). Of the normal, nonatherosclerotic components of the vessel wall, adventitia had the highest platelet deposition, subendothelium had the lowest, and tunica media had an intermediate thrombogenicity. These observations suggest a direct relationship between the severity of injury and acute thrombotic response in nonatherosclerotic arterial substrates.
|
Morphological and Dig-FVIIa Binding on the Different Types of Human Atherosclerotic Plaques
Representative sections stained for Dig-FVIIa binding and the corresponding trichrome-stained sections of human atherosclerotic lesions are shown in Fig 3. Among all the studied atherosclerotic lesions, those containing a lipid-rich core exhibited the most intense TF staining (3±0.1 AU) compared with both normal and arteriosclerotic segments (adventitia, 2±0.1 AU; foam cell–rich matrix, 2±0.01; tunica media, 1±0.3; collagen matrix, 1±0.001; and normal intima, 1±0.1). Adventitia had the highest score for intensity of TF staining of all the normal, nonatherosclerotic specimens. In addition, when all available specimens were analyzed microscopically, the amount of Dig-FVIIa staining increased with the progression of atherosclerotic lesions from foam cell rich with predominantly intracellular lipids to the more advanced lesions characterized by abundant cholesterol crystals (Fig 3). Finally, statistical analysis of all specimens showed a positive correlation between the number of platelets deposited and TF score (P<.01) (Fig 2
).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Arterial injury activates the intrinsic pathway of blood coagulation to maintain the integrity of the vascular system. In addition, the extrinsic pathway of the coagulation is also initiated by exposure of flowing blood to TF, the cellular "receptor" and cofactor for factor VII, leading, through thrombin generation and fibrin deposition, to thrombus formation.
The present study provides evidence of TF involvement in platelet deposition and thrombus formation on disrupted human atherosclerotic lesions exposed to flowing blood in a well-controlled perfusion system. Under the same experimental conditions, we previously demonstrated that the lipid-rich atheromatous core from human atherosclerotic plaques is the most thrombogenic substrate, and platelet deposition on this substrate is up to sixfold higher than on other types of lesions, including adventitia and collagen-rich matrix.9 This observation has important pathophysiological and clinical implications. Histopathologic data show that the so-called "vulnerable plaques," the most prone to rupture, are characterized by an eccentric, lipid-rich core usually separated from flowing blood by a thin fibrous cap. Disrupted atherosclerotic lesions are often associated with thrombus formation on their luminal surface. This type of lesion is responsible for triggering acute coronary syndromes.3 4 5 6 18 19 By contrast, collagen-rich fibrotic plaques are more stable, and resultant thrombotic complications are often the result of a decreased blood flow due to the stenosis of the vessel.1 2 20 21
In the present study, the inner components of human atherosclerotic plaque were artificially exposed to flowing blood to mimic spontaneous plaque disruption. We found that the lipid-rich core is a more potent stimulus for thrombus formation than fibrous, collagen-rich lesions. This does not lessen the importance of the collagen matrix, which, after plaque disruption, may also activate platelet deposition and the coagulation cascade.22 23
In contrast to our data, van Zanten et al,24 using arterial cross sections mounted in a rectangular perfusion chamber, reported strong platelet deposition on collagen-rich connective tissue and adventitia with little reactivity to the lipid core of the plaque. The lack of platelet deposition on lipid-rich atherosclerotic plaques observed by those investigators may relate to their different experimental conditions. One possible reason for the discrepancies between the latter and our results and those clinically observed may be the anticoagulation (citrate or low-molecular-weight heparin with or without hirudin) and sample manipulation used by van Zanten et al, which may induce differences in thrombin generation and/or function in their perfusion system. In fact, they found that platelet deposition was significantly reduced by antibodies to von Willebrand factor but was not affected by RGDW peptides. We25 recently demonstrated that local thrombin generation plays an important role in platelet deposition and thrombus growth on areas of severe vessel wall damage. We found that hirudin added to heparinized blood reduced platelet deposition to the severely injured wall but not to collagen-coated slides. In addition, hirudin added to citrated blood did not further decrease platelet deposition, which suggests that local thrombin generation plays a role in platelet deposition in heparinized conditions and that thrombin activity is completely blocked in citrated blood by chelating calcium. Furthermore, platelet deposition on collagen fibrils is not mediated by thrombin,24 which suggests other biochemical mechanisms for platelet interaction with this substrate.
In the present study, we also observed that the components of the nonatherosclerotic arterial wall were significantly less thrombogenic than the lipid-rich core of atherosclerotic plaque. Among these normal structures, adventitia appeared to be the most thrombogenic and intima the least, and tunica media showed an intermediate degree of thrombogenicity. These findings agree with previous data from animal models26 27 that indicate that the degree of thrombus formation and its persistence after balloon angioplasty depend on the depth of the vascular injury induced by the procedure, which suggests that the thrombogenicity of deeper vascular structures plays an important role in acute reocclusion and late restenosis after coronary interventions.
The exact mechanism(s) responsible for the thrombogenic properties of the various atherosclerotic plaque components, and particularly of the lipid-rich core, is still uncertain. Lipids alone (crystalline structures, phospholipids, or soft lipids) or cellular degradation products in the core were proposed as possible activators of the hemostatic system.28 Among cellular-derived products, TF has been proposed as a major candidate.10 Previous studies29 30 showed that thrombogenicity in a flow system of cultured fibroblasts, smooth muscle cells, and their elaborated matrices is related to TF activity and that the prothrombotic properties of these cells can be blocked by antibodies against TF. Expression of TF antigen by vascular cells has also been identified by immunohistochemistry in both normal and atherosclerotic human vessels,12 13 31 32 especially in the necrotic core surrounding cholesterol clefts in atherosclerotic plaques from human carotid endarterectomy specimens.12 However, no evidence has been presented of the ability of the TF protein to trigger coagulation. By the in situ assay used in this study, we demonstrated that Dig-FVIIa binding sites are highly expressed in the relatively acellular lipid core of atherosclerotic lesions, and a strong correlation exists between Dig-FVIIa staining and platelet deposition on both normal and diseased components of human plaque exposed to flowing blood. Thus, we provide evidence that the increased thrombogenicity of atheromatous lesions, disrupted spontaneously or by angioplasty, may be mediated by TF.
The origin of the TF found in the lipid-rich core of atherosclerotic lesions is poorly understood. It has been suggested that monocyte/macrophage–type cells such as foam cells play a crucial role in the early formation of atherosclerotic plaque and its evolution into a lesion prone to disruption.33 34 35 36 The expression of TF by monocytes and macrophage-derived foam cells has been recently demonstrated in atherosclerotic lesions,12 and TF-mediated procoagulant activity was shown in adherent human peripheral blood monocytes under flow conditions.37 Moreover, the expression of functional TF by human monocytes is stimulated by oxidized low-density lipoproteins present in atheromatous plaque.38 These observations suggest that TF found in the lipid-rich core of atherosclerotic lesions is largely derived from macrophages present in the plaque.39 However, we cannot rule out the possible contribution of smooth muscle cells and even endothelial cells.
Finally, our work has important therapeutic implications. Inhibition of the TF pathway of coagulation by specific anti-TF antibodies,40 41 factor VIIa inhibitors,42 or the recombinant form of its physiological inhibitor, TF pathway inhibitor, was shown to be effective for prevention of arterial thrombosis in several animal models.43 44 Such approaches may offer promising new tools for preventing reocclusion after successful thrombolysis or thrombotic occlusion in patients with unstable angina and after percutaneous coronary angioplasty.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
We gratefully acknowledge Dr Adrian Padurean for his technical expertise in the preparation of the animal models and Veronica Gulle for her skillful help in the processing and staining of the specimens.
|
Footnotes |
|---|
Dr Toschi's current address is Dipartimento di Ematologia e Trafusionale, Ospedale S. Carlo Borromeo, Via Pio II, 320153 Milano, Italy. Dr Lettino's current address is Primario Divisione di Cardiologia e UCIC, Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20100 Milano, Italy.
Received May 15, 1996; revision received September 9, 1996; accepted September 12, 1996.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med. 1994;326:242-250.[Medline] [Order article via Infotrieve]
2. Badimon JJ, Fuster V, Chesebro JH, Badimon L. Coronary atherosclerosis: a multifactorial disease. Circulation. 1993;87(suppl II):II-3-II-16.
3.
Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657-671.
4.
Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis: characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J. 1983;50:127-134.
5.
Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Circulation. 1985;71:699-708.
6.
Davies M, Thomas AC. Plaque fissuring: the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J. 1985;53:363-373.
7. Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M, Borrico S, Goblin R, Fuster V. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1988;12:56-62.[Abstract]
8. Mizuno K, Satomura K, Miyamoto A, Arakawa K, Shibuya T, Arai T, Kurita A, Nakamura H, Ambrose JA. Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes. N Engl J Med. 1992;326:287-291.[Abstract]
9. Fernandez-Ortiz A, Badimon JJ, Falk E, Fuster V, Meyer B, Mailhac A, Weng D, Shah PK, Badimon L. Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol. 1994;23:1562-1569.[Abstract]
10. Rapaport SI, Rao VM. Initiation and regulation of tissue factor–dependent blood coagulation. Arterioscler Thromb. 1992;12:1111-1121.[Medline] [Order article via Infotrieve]
11.
Nemerson Y. Tissue factor and hemostasis. Blood. 1988;71:1-8.
12.
Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci U S A. 1989;86:2839-2843.
13.
Annex BH, Denning SM, Channon KM, Sketch MH Jr, Stack RS, Morrisey JH, Peters KG. Differential expression of tissue factor protein in directional atherectomy specimens from patients with stable and unstable coronary syndromes. Circulation. 1995;91:619-622.
14. Thiruvikraman SV, Guha A, Rebos R, Nemerson Y, Fallon JT. In situ localization of tissue factor in human atherosclerotic plaques by binding of digoxigenin labeled factors VIIa and X. Lab Invest. 1996;75:451-461.[Medline] [Order article via Infotrieve]
15.
Badimon L, Badimon JJ, Galvez A, Chesebro JH, Fuster V. Influence of arterial damage and wall shear rate on platelet deposition: ex vivo study in a swine model. Arteriosclerosis. 1986;6:312-320.
16.
Badimon L, Badimon JJ, Turitto V, Vallabhajosula S, Fuster V. Platelet thrombus formation on collagen type I: a model of deep vessel injury—influence of blood rheology, von Willebrand factor blood coagulation. Circulation. 1988;78:1431-1442.
17. Badimon L, Fuster V, Chesebro JH, Dewanjee MK. New `ex vivo' radioisotopic method of quantification of platelet deposition: studies in four animal species. Thromb Haemost. 1983;50:639-644.[Medline] [Order article via Infotrieve]
18. Arbustini E, Grasso M, Diegoli M, Pucci A, Bramerio M, Ardissino D, Angoli L, de Servi S, Bramucci E, Mussini A, Vigano M, Specchia G. Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. Am J Cardiol. 1991;69:36B-50B.
19.
Davies M, Richardson PD, Woolf N, Katz DR, Mann J. Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J. 1993;69:377-381.
20.
Kragel AH, Reddy SG, Wittes JT, Roberts WC. Morphometric analysis of the composition of atherosclerotic plaques in the four major epicardial coronary arteries in acute myocardial infarction and sudden coronary death. Circulation. 1989;80:1747-1756.
21. Kragel AH, Gertz SD, Roberts WC. Morphologic comparison of frequency and types of acute lesions in the major epicardial coronary arteries in unstable angina pectoris, sudden coronary death and acute myocardial infarction. J Am Coll Cardiol. 1991;18:801-808.[Abstract]
22. Badimon L, Chesebro JH, Badimon JJ. Thrombus formation on ruptured atherosclerotic plaques and rethrombosis on evolving thrombi. Circulation. 1992;86(suppl I):III-74-III-85.
23. Chesebro JH, Webster MW, Zoldhelyi P, Roche PC, Badimon L, Badimon JJ. Antithrombotic therapy and progression of coronary artery disease: antiplatelet versus antithrombins. Circulation. 1992;86(suppl I):III-100-III-111.
24. van Zanten GH, de Graaf S, Slootweg PJ, Heijnen HFG, Connolly TM, de Groot PG, Sixma JJ. Increased platelet deposition on atherosclerotic coronary arteries. J Clin Invest. 1994;93:615-632.
25.
Badimon L, Badimon JJ, Lassila R, Heras M, Chesebro JH, Fuster V. Thrombin regulation of platelet interaction with damaged vessel wall and isolated collagen type I at arterial flow conditions in a porcine model: effects of hirudins, heparin, and calcium chelation. Blood. 1991;78:423-434.
26.
Steele P, Chesebro JH, Stanson AW, Holmes DR, Dewanjee MK, Badimon L, Fuster V. Balloon angioplasty: natural history of the pathophysiologic response to injury in a pig model. Circ Res. 1985;57:105-112.
27. Ip JH, Fuster V, Israel D, Badimon L, Badimon JJ, Chesebro JH. The role of platelets, thrombin and hyperplasia in restenosis after coronary angioplasty. J Am Coll Cardiol. 1991;17:77B-88B.
28. Guyton JR, Klemp KF. The lipid-rich core region of human atherosclerotic fibrous plaques: prevalence of small lipid droplets and vesicles by electron microscopy. Am J Pathol. 1989;134:705-717.[Abstract]
29.
Grabowski EF, Zucherman DB, Nemerson Y. The functional expression of tissue factor by fibroblasts and endothelial cells under flow conditions. Blood. 1993;81:3265-3270.
30.
Zwaginga JJ, de Boer HC, Ijsseldijk MJW, Kerkhof A, Muller-Berghaus G, Gruhlichhenn J, Sixma JJ, de Groot PG. Thrombogenicity of vascular cells: comparison between endothelial cells isolated from different sources and smooth muscle cells and fibroblasts. Arteriosclerosis. 1990;10:437-448.
31. Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues: implications for disorders of hemostasis and thrombosis. Am J Pathol. 1989;134:1087-1097.[Abstract]
32. Fleck RA, Rao LVM, Rapaport SI, Varki N. Localization of human tissue factor antigen by immunostaining with monospecific, polyclonal anti-human tissue factor antibody. Thromb Res. 1990;57:765-781.
33.
Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes. Circulation. 1994;90:775-778.
34.
van der Waal A, Becker A, van der Loos C, Das P. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of dominant plaque morphology. Circulation. 1994;89:36-45.
35.
Galis ZS, Sukhova GK, Kranzhofer R, Clark S, Libby P. Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci U S A. 1995;92:402-406.
36. Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A, Mailhac A, Villarreal-Levy G, Fallon JT, Regnstrom J, Fuster V. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Circulation. 1995;92:1565-1569.
37.
Barstad RM, Hamers MJAG, Kierulf P, Westvik A-B, Sakariassen KS. Procoagulant human monocytes mediate tissue factor/factor VIIa-dependent platelet-thrombus formation when exposed to flowing nonanticoagulated human blood. Arterioscler Thromb Vasc Biol. 1995;15:11-16.
38.
Brand K, Banka CL, Mackman N, Terkeltaub RA, Fan S-T, Curtiss LK. Oxidized LDL enhances lipopolysaccharide-induced tissue factor expression in human adherent monocytes. Arterioscler Thromb. 1994;14:790-797.
39. Rao LVM, Robinson T, Hoang AD. Factor VIIa/tissue factor-catalyzed activation of factor IX and X on cell surface and in suspension: a kinetic study. Thromb Haemost. 1992;67:654-659.[Medline] [Order article via Infotrieve]
40.
Pawashe AB, Golino P, Ambrosio G, Migliaccio F, Ragni M, Pascucci I, Chiariello M, Bach R, Garen A, Konigsberg W, Ezekowitz MD. A monoclonal antibody against rabbit tissue factor inhibits thrombus formation in stenotic injured rabbit carotid arteries. Circ Res. 1994;74:56-63.
41.
Weiss H, Turitto H, Baumgartner H, Nemerson Y, Hoffman T. Evidence for the presence of tissue factor activity on subendothelium. Blood. 1989;73:968-975.
42.
Jang Y, Guzman L, Lincoff M, Gottsauner-Wol M, Forudi F, Hart CE, Courtman DW, Ezban M, Ellis S, Topol E. Influence of blockade at specific levels of the coagulation cascade on restenosis in a rabbit atherosclerotic femoral artery injury model. Circulation. 1995;92:3041-3050.
43.
Haskel EJ, Torr SR, Day KC, Palmier MO, Wun TC, Sobel BE, Abendscheim D. Prevention of arterial reocclusion after thrombolysis with tPA with recombinant lipoprotein-associated coagulation inhibitor. Circulation. 1991;84:821-827.
44. Badimon JJ, Lettino M, Toschi V, Gallo R, Fallon JT, Nemerson Y, Badimon L, Chesebro JH. Inhibitory effects of TFPI on platelet-thrombus formation triggered by lipid-rich human atherosclerotic plaque. Circulation. 1995;92(suppl I):I-693. Abstract.
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]
|
|
|
|
 |
|
 D. A. Vorchheimer and R. Becker Platelets in Atherothrombosis Mayo Clin. Proc., January 1, 2006; 81(1): 59 - 68. [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. Loffredo, and M. Chiariello Expression of exogenous tissue factor pathway inhibitor in vivo suppresses thrombus formation in injured rabbit carotid arteries J. Am. Coll. Cardiol., August 1, 2001; 38(2): 569 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.F. Bentzon and E. Falk Coronary plaques calling for action -- why, where and how many? Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I3 - I9. [Abstract] [PDF]
|
|
|
|
|
|
L. Badimon, G. Vilahur, S. Sanchez, and X. Duran Atheromatous plaque formation and thrombogenesis: formation, risk factors and therapeutic approaches Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I16 - I22. [Abstract] [PDF]
|
|
|
|
|
|
R. Corti, Z. A. Fayad, V. Fuster, S. G. Worthley, G. Helft, J. Chesebro, M. Mercuri, and J. J. Badimon Effects of Lipid-Lowering by Simvastatin on Human Atherosclerotic Lesions: A Longitudinal Study by High-Resolution, Noninvasive Magnetic Resonance Imaging Circulation, July 17, 2001; 104(3): 249 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Westrick, P. F. Bodary, Z. Xu, Y.-C. Shen, G. J. Broze, and D. T. Eitzman Deficiency of Tissue Factor Pathway Inhibitor Promotes Atherosclerosis and Thrombosis in Mice Circulation, June 26, 2001; 103(25): 3044 - 3046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. G. Turpie and E. M. Antman Low-Molecular-Weight Heparins in the Treatment of Acute Coronary Syndromes Arch Intern Med, June 25, 2001; 161(12): 1484 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Friederich, M. Levi, K. A. Bauer, G. P. Vlasuk, W. E. Rote, D. Breederveld, T. Keller, M. Spataro, S. Barzegar, and H. R. Buller Ability of Recombinant Factor VIIa to Generate Thrombin During Inhibition of Tissue Factor in Human Subjects Circulation, May 29, 2001; 103(21): 2555 - 2559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Mallat and A. Tedgui Current Perspective on the Role of Apoptosis in Atherothrombotic Disease Circ. Res., May 25, 2001; 88(10): 998 - 1003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
K. P. Rentrop Thrombi in Acute Coronary Syndromes : Revisited and Revised Circulation, April 4, 2000; 101(13): 1619 - 1626. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||