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The role of smooth muscle derived tissue factor in mediating thrombosis and arterial injury1
Thrombosis Research (2008) 122 Suppl. 1, S78–S81
intl.elsevierhealth.com/journals/thre
The role of smooth muscle derived tissue factor in mediating thrombosis and arterial injury1 Mark B. Taubman*, Li Wang, Christine Miller Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester, Rochester, NY, USA
KEYWORDS Tissue factor Smooth muscle cells Intimal hyperplasia Thrombosis
Abstract Tissue factor (TF) is a glycoprotein that initiates coagulation, regulates hemostasis and plays a critical role in arterial thrombosis. Vascular smooth muscle cells (SMC) are the major cellular component of the arterial wall. Under normal conditions, SMC express minimal levels of TF; however TF is rapidly induced in SMC by growth factors and cytokines and is expressed in abundance in arterial SMC in response to injury and during atherogenesis. Recent studies have suggested that SMC-derived TF plays an important role in promoting arterial thrombosis and in mediating intimal hyperplasia in response to arterial injury. This latter role may be related to non-procoagulant properties of TF. © 2008 Elsevier Ltd. All rights reserved.
Introduction Tissue factor (TF) is a glycoprotein that initiates coagulation, regulates hemostasis and plays a critical role in mediating arterial thrombosis [1,2]. TF is constitutively and inducibly expressed by many cell types, including monocyte/ macrophages, adventitial fibroblasts, endothelial cells, cardiomyocytes, and smooth muscle cells (SMC) that are in contact with circulating blood. This review focuses on the role of SMC-derived TF in mediating thrombosis and arterial injury. TF mRNA is expressed at low levels in cultured SMC, but is induced as a primary response to a variety of growth factors and cytokines, including platelet-derived growth factor (PDGF), * Corresponding author. Mark B. Taubman, M.D. 601 Elmwood Ave, Box 679, Rochester, NY 14642, USA. Tel.: +1 585 275 9905; fax: +1 585 276 1917. E-mail address: [email protected] (M.B. Taubman).
angiotensin II, thrombin, and tumor necrosis factor-a, molecules that have been implicated in activating SMC to a proliferative and inflammatory state [3]. Inflammatory chemokines, such as monocyte chemoattractant protein-1, macrophage inflammatory protein-1 and stromal derived factor-1, also induce TF in SMC (reviewed in [4]). Active TF is found transiently on the surface of agonist-treated SMC and is also released from SMC in microparticles that accumulate in the culture medium [5]. Similar to cell culture, TF mRNA, antigen, and activity are found at low levels in normal arterial media, but are rapidly induced after arterial injury in medial SMC, and subsequently accumulate in the SMC of the resulting neointima (references in [6]). TF is also abundant in atherosclerotic plaques, particularly in macrophages, intimal SMC, and the lipid-rich necrotic core [7]. It has generally been thought that arterial thrombosis occurs when TF induced
1 All authors have made substantial contributions to all of the following: (1) the conception and design of studies, or acquisition of data described in the review, (2) drafting the article or revising it critically for important intellectual content, and (3) final approval of the version submitted.
0049-3848/ $ – see front matter © 2008 Elsevier Ltd. All rights reserved.
The role of smooth muscle derived tissue factor in mediating thrombosis and arterial injury by injury to the arterial surface or exposed by plaque rupture comes into contact with blood coagulant factors. Recent studies have demonstrated that TF is always present in the circulation, mostly in microparticles that presumably bud from the cell membrane as part of normal homeostasis or are released from intracellular stores as a consequence of necrosis or apoptosis (reviewed in [2]). Although the cellular sources of circulating TF have not been precisely defined, platelets, monocyte/macrophages, and endothelial cells are important contributors. Increased levels of circulating TF have been found in patients with acute coronary syndromes, diffuse intravascular coagulopathy, endotoxemia, and cancer (reviewed in [2]). SMC-derived TF and thrombosis Thrombosis is a major cause of morbidity and mortality. Studies using inhibitors of TF activity, including antibodies to TF [8,9], active siteinactivated factor VIIa [10], and tissue factor pathway inhibitor (TFPI) [11,12] have provided evidence that TF plays a critical role in mediating arterial thrombosis. However, the relative contributions of arterial wall and circulating TF to thrombosis remain controversial. Although some studies have suggested that circulating TF contributes to thrombus generation [13,14], others have suggested that the levels of TF in human blood are too low to be clinically important [15]. Using intravital microscopy, Furie and colleagues demonstrated that circulating TF accumulates in the developing thrombus and contributes to fibrin formation in a microvascular thrombosis model involving laser injury of cremaster arterioles [13]. Total TF deletion in mice results in intrauterine lethality. However, TF-null embryos can be rescued with a minigene containing the human TF promoter and cDNA. These mice (referred to as low-TF mice) express 1% of TF activity when compared with wild-type mice and have decreased thrombosis in response to carotid arterial injury [16]. Transplanting bone marrow from low-TF mice into wild-type mice decreased the size of thrombus induced by laser injury to cremaster arterioles, when compared with mice receiving wild-type marrow [13], suggesting an important role for bone marrow-derived circulating TF in thrombus formation. In contrast, a similar bone marrow transplantation strategy, employing Rose Bengal injury of the carotid artery, suggested that thrombosis of large arteries was not dependent on bone marrow-derived TF
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and therefore was presumably dependent on TF present in medial SMC [16]. To provide further insights into the role of arterial wall and circulating TF in mediating arterial thrombosis, and to examine specifically the role of VSMC in this process, we have recently generated SMC-specific TF-deficient mice. These mice have a >95% decrease in aortic medial TF mRNA and activity, but have similar levels of circulating TF activity compared to wild-type animals. SMC-specific TF deficiency was not accompanied by abnormalities in hemostasis, as measured by tail vein bleeding, but was associated with marked impairment in thrombosis after ferric chloride injury of the carotid artery [Wang L, Mackman N, Taubman MB, unpublished observations]. These data support those generated in the Rose Bengal model using low-TF mice and suggest that SMC-derived medial TF but not circulating TF may be critical for thrombosis in large arteries under conditions associated with endothelial denudation and exposure of the underlying SMC, such as those produced by human percutaneous coronary interventions. In contrast, circulating TF may contribute importantly to microvascular thrombosis, such as that produced by laser injury. Additional experiments will be needed in a wider array of models to better establish the relative contributions of SMCderived arterial wall TF and circulating TF to intravascular thrombosis. SMC-derived TF and the response to arterial injury Studies using inhibitors of TF activity, such as inactivated factor VIIa, TFPI or TF antibodies, have provided evidence that TF plays a key role in mediating intimal hyperplasia and luminal narrowing in response to arterial injury in mouse, rat, rabbit, and porcine models (reviewed in [6]). Low-TF mice also displayed a marked reduction in intimal hyperplasia in response to femoral artery injury [17]. SMC-specific TF-deficient mice have a similar reduction (~60%) in I/M ratio in response to arterial injury, suggesting that TF present in the SMC of the arterial wall, rather than from circulating sources, may be largely responsible for TF-mediated regulation of intimal hyperplasia [Wang L, Mackman N, Taubman MB, unpublished observations]. Many models of arterial injury are associated with little or no thrombus formation (particularly those involving rodents). This raises the question as to whether TF mediates changes in the arterial wall independent of its role in thrombosis. A number of studies have suggested
S80 that TF mediates migration of SMC or fibroblasts. Factor VIIa enhances PDGF-mediated migration of cultured fibroblasts [18] and induces migration of mouse SMC, whereas isolated TF:VIIa complexes induce SMC migration [19]. SMC derived from low-TF mice had a 71% decrease in migration in a modified Boyden chamber in response to 10% fetal bovine serum. The precise mechanism by which TF mediates SMC migration remains to be determined. Because TF has a transmembrane-spanning domain and a cytoplasmic tail, it has the potential to be involved in transmembrane signaling. This could in part explain the effects of TF inhibition on intimal hyperplasia. The cytoplasmic domain of TF interacts with actin binding protein 280 to mediate cytoskeletal arrangement and cell spreading [20]. The cytoplasmic domain has also been implicated in tumor metastasis (reviewed in [21]), although the mechanism remains to be determined. Products of TF-dependent activation of the coagulation cascade have direct cellular effects. Thrombin regulates growth, migration, and the synthesis of inflammatory mediators and receptors in SMC, and has been implicated in the progression of atherosclerosis and in the response to arterial injury (reviewed in [22]). Factor VIIa induces a variety of intracellular signals associated with cell growth and migration, including mobilization of intracellular Ca2+ , activation of phospholipase C, and induction of mitogenactivated protein (MAP) and Src kinases. Many of these effects are dependent upon TF, but independent of its cytoplasmic domain [23,24]. Protease activated receptor (PAR)2 has been implicated in VIIa-mediated cell activation [25], as has a receptor distinct from the PARs [26]. Factor Xa has also been implicated in cell proliferation and induces signals associated with proliferation and migration, similar to those described above (referenced in [27]). Summary In summary, current data suggest that SMCderived TF is likely to play a critical role in mediating arterial thrombosis and the intimal response to arterial injury. In addition, SMC are a major source of TF in atherosclerotic plaques and are thus likely to be involved in mediating thrombosis associated with plaque rupture. The availability of new animal models should allow for a more precise definition of the relative contribution of SMC-derived TF and circulating TF to these processes. Local inhibition of SMCderived arterial TF may be worth considering as
M.B. Taubman et al. a novel approach to inhibiting intimal hyperplasia and thrombosis associated with percutaneous vascular interventions. Conflict of interest statement None of the authors have a conflict of interest. References [1] Nemerson Y. Tissue factor: then and now. Thromb Haemost 1995;74(1):180 4. [2] Mackman N. Role of tissue factor in hemostasis and thrombosis. Blood Cells Mol Dis 2006;36(2):104 7. [3] Taubman MB. Tissue factor regulation in vascular smooth muscle: a summary of studies performed using in vivo and in vitro models. Am J Cardiol 1993;72(8):55C 60C. [4] Schecter AD, Berman AB, Taubman MB. Chemokine receptors in vascular smooth muscle. Microcirculation 2003;10(3 4):265 72. [5] Schecter AD, Spirn B, Rossikhina M, Giesen PL, Bogdanov V, Fallon JT, et al. Release of active tissue factor by human arterial smooth muscle cells. Circ Res 2000;87(2): 126 32. [6] Taubman MB, Giesen PL, Schecter AD, Nemerson Y. Regulation of the procoagulant response to arterial injury. Thromb Haemost 1999;82(2):801 5. [7] Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1989;86(8):2839 43. [8] Jang IK, Gold HK, Leinbach RC, Fallon JT, Collen D, Wilcox JN. Antithrombotic effect of a monoclonal antibody against tissue factor in a rabbit model of platelet-mediated arterial thrombosis. Arterioscler Thromb 1992;12(8):948 54. [9] Pawashe AB, Golino P, Ambrosio G, Migliaccio F, Ragni M, Pascucci I, et al. A monoclonal antibody against rabbit tissue factor inhibits thrombus formation in stenotic injured rabbit carotid arteries. Circ Res 1994;74(1):56 63. [10] Golino P, Ragni M, Cirillo P, D’Andrea D, Scognamiglio A, Ravera A, et al. Antithrombotic effects of recombinant human, active site-blocked factor VIIa in a rabbit model of recurrent arterial thrombosis. Circ Res 1998;82(1):39 46. [11] Asada Y, Hara S, Tsuneyoshi A, Hatakeyama K, Kisanuki A, Marutsuka K, et al. Fibrin-rich and plateletrich thrombus formation on neointima: recombinant tissue factor pathway inhibitor prevents fibrin formation and neointimal development following repeated balloon injury of rabbit aorta. Thromb Haemost 1998;80(3): 506 11. [12] Roque M, Reis ED, Fuster V, Padurean A, Fallon JT, Taubman MB, et al. Inhibition of tissue factor reduces thrombus formation and intimal hyperplasia after porcine coronary angioplasty. J Am Coll Cardiol 2000;36(7):2303 10. [13] Chou J, Mackman N, Merrill-Skoloff G, Pedersen B, Furie BC, Furie B. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004;104(10):3190 7. [14] Giesen PL, Rauch U, Bohrmann B, Kling D, Roque M, Fallon JT, et al. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 1999;96(5):2311 5. [15] Butenas S, Mann KG. Active tissue factor in blood? Nat Med 2004;10(11):1155 6; author reply 1156.
The role of smooth muscle derived tissue factor in mediating thrombosis and arterial injury [16] Day SM, Reeve JL, Pedersen B, Farris DM, Myers DD, Im M, et al. Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall. Blood 2005; 105(1):192 8. [17] Pyo R, Jensen KK, Wiekowski MT, Manfra D, Alcami A, Taubman MB, et al. Inhibition of intimal hyperplasia in transgenic mice conditionally expressing the chemokinebinding protein M3. Am J Pathol 2004;164(6):2289 97. [18] Siegbahn A, Johnell M, Rorsman C, Ezban M, Heldin CH, Ronnstrand L. Binding of factor VIIa to tissue factor on human fibroblasts leads to activation of phospholipase C and enhanced PDGF-BB-stimulated chemotaxis. Blood 2000;96(10):3452 8. [19] Sato Y, Asada Y, Marutsuka K, Hatakeyama K, Kamikubo Y, Sumiyoshi A. Tissue factor pathway inhibitor inhibits aortic smooth muscle cell migration induced by tissue factor/factor VIIa complex. Thromb Haemost 1997;78(3): 1138 41. [20] Ruf W. Tissue factor-dependent signaling in tumor biology. Pathophysiol Haemost Thromb 2003;33(Suppl 1):28 30. [21] Belting M, Ahamed J, Ruf W. Signaling of the tissue factor coagulation pathway in angiogenesis and cancer. Arterioscler Thromb Vasc Biol 2005;25(8):1545 50.
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[22] Patterson C, Stouffer GA, Madamanchi N, Runge MS. New tricks for old dogs: nonthrombotic effects of thrombin in vessel wall biology. Circ Res 2001;88(10):987 97. [23] Camerer E, Rottingen JA, Gjernes E, Larsen K, Skartlien AH, Iversen JG, et al. Coagulation factors VIIa and Xa induce cell signaling leading to up-regulation of the egr-1 gene. J Biol Chem 1999;274(45):32225 33. [24] Petersen LC, Freskgard P, Ezban M. Tissue factordependent factor VIIa signaling. Trends Cardiovasc Med 2000;10(2):47 52. [25] Camerer E, Huang W, Coughlin SR. Tissue factorand factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci USA 2000;97(10):5255 60. [26] Petersen LC, Thastrup O, Hagel G, Sorensen BB, Freskgard PO, Rao LV, et al. Exclusion of known protease-activated receptors in factor VIIa-induced signal transduction. Thromb Haemost 2000;83(4):571 6. [27] McLean K, Schirm S, Johns A, Morser J, Light DR. FXainduced responses in vascular wall cells are PAR-mediated and inhibited by ZK-807834. Thromb Res 2001;103(4): 281 97.
intl.elsevierhealth.com/journals/thre
The role of smooth muscle derived tissue factor in mediating thrombosis and arterial injury1 Mark B. Taubman*, Li Wang, Christine Miller Aab Cardiovascular Research Institute and Department of Medicine, University of Rochester, Rochester, NY, USA
KEYWORDS Tissue factor Smooth muscle cells Intimal hyperplasia Thrombosis
Abstract Tissue factor (TF) is a glycoprotein that initiates coagulation, regulates hemostasis and plays a critical role in arterial thrombosis. Vascular smooth muscle cells (SMC) are the major cellular component of the arterial wall. Under normal conditions, SMC express minimal levels of TF; however TF is rapidly induced in SMC by growth factors and cytokines and is expressed in abundance in arterial SMC in response to injury and during atherogenesis. Recent studies have suggested that SMC-derived TF plays an important role in promoting arterial thrombosis and in mediating intimal hyperplasia in response to arterial injury. This latter role may be related to non-procoagulant properties of TF. © 2008 Elsevier Ltd. All rights reserved.
Introduction Tissue factor (TF) is a glycoprotein that initiates coagulation, regulates hemostasis and plays a critical role in mediating arterial thrombosis [1,2]. TF is constitutively and inducibly expressed by many cell types, including monocyte/ macrophages, adventitial fibroblasts, endothelial cells, cardiomyocytes, and smooth muscle cells (SMC) that are in contact with circulating blood. This review focuses on the role of SMC-derived TF in mediating thrombosis and arterial injury. TF mRNA is expressed at low levels in cultured SMC, but is induced as a primary response to a variety of growth factors and cytokines, including platelet-derived growth factor (PDGF), * Corresponding author. Mark B. Taubman, M.D. 601 Elmwood Ave, Box 679, Rochester, NY 14642, USA. Tel.: +1 585 275 9905; fax: +1 585 276 1917. E-mail address: [email protected] (M.B. Taubman).
angiotensin II, thrombin, and tumor necrosis factor-a, molecules that have been implicated in activating SMC to a proliferative and inflammatory state [3]. Inflammatory chemokines, such as monocyte chemoattractant protein-1, macrophage inflammatory protein-1 and stromal derived factor-1, also induce TF in SMC (reviewed in [4]). Active TF is found transiently on the surface of agonist-treated SMC and is also released from SMC in microparticles that accumulate in the culture medium [5]. Similar to cell culture, TF mRNA, antigen, and activity are found at low levels in normal arterial media, but are rapidly induced after arterial injury in medial SMC, and subsequently accumulate in the SMC of the resulting neointima (references in [6]). TF is also abundant in atherosclerotic plaques, particularly in macrophages, intimal SMC, and the lipid-rich necrotic core [7]. It has generally been thought that arterial thrombosis occurs when TF induced
1 All authors have made substantial contributions to all of the following: (1) the conception and design of studies, or acquisition of data described in the review, (2) drafting the article or revising it critically for important intellectual content, and (3) final approval of the version submitted.
0049-3848/ $ – see front matter © 2008 Elsevier Ltd. All rights reserved.
The role of smooth muscle derived tissue factor in mediating thrombosis and arterial injury by injury to the arterial surface or exposed by plaque rupture comes into contact with blood coagulant factors. Recent studies have demonstrated that TF is always present in the circulation, mostly in microparticles that presumably bud from the cell membrane as part of normal homeostasis or are released from intracellular stores as a consequence of necrosis or apoptosis (reviewed in [2]). Although the cellular sources of circulating TF have not been precisely defined, platelets, monocyte/macrophages, and endothelial cells are important contributors. Increased levels of circulating TF have been found in patients with acute coronary syndromes, diffuse intravascular coagulopathy, endotoxemia, and cancer (reviewed in [2]). SMC-derived TF and thrombosis Thrombosis is a major cause of morbidity and mortality. Studies using inhibitors of TF activity, including antibodies to TF [8,9], active siteinactivated factor VIIa [10], and tissue factor pathway inhibitor (TFPI) [11,12] have provided evidence that TF plays a critical role in mediating arterial thrombosis. However, the relative contributions of arterial wall and circulating TF to thrombosis remain controversial. Although some studies have suggested that circulating TF contributes to thrombus generation [13,14], others have suggested that the levels of TF in human blood are too low to be clinically important [15]. Using intravital microscopy, Furie and colleagues demonstrated that circulating TF accumulates in the developing thrombus and contributes to fibrin formation in a microvascular thrombosis model involving laser injury of cremaster arterioles [13]. Total TF deletion in mice results in intrauterine lethality. However, TF-null embryos can be rescued with a minigene containing the human TF promoter and cDNA. These mice (referred to as low-TF mice) express 1% of TF activity when compared with wild-type mice and have decreased thrombosis in response to carotid arterial injury [16]. Transplanting bone marrow from low-TF mice into wild-type mice decreased the size of thrombus induced by laser injury to cremaster arterioles, when compared with mice receiving wild-type marrow [13], suggesting an important role for bone marrow-derived circulating TF in thrombus formation. In contrast, a similar bone marrow transplantation strategy, employing Rose Bengal injury of the carotid artery, suggested that thrombosis of large arteries was not dependent on bone marrow-derived TF
S79
and therefore was presumably dependent on TF present in medial SMC [16]. To provide further insights into the role of arterial wall and circulating TF in mediating arterial thrombosis, and to examine specifically the role of VSMC in this process, we have recently generated SMC-specific TF-deficient mice. These mice have a >95% decrease in aortic medial TF mRNA and activity, but have similar levels of circulating TF activity compared to wild-type animals. SMC-specific TF deficiency was not accompanied by abnormalities in hemostasis, as measured by tail vein bleeding, but was associated with marked impairment in thrombosis after ferric chloride injury of the carotid artery [Wang L, Mackman N, Taubman MB, unpublished observations]. These data support those generated in the Rose Bengal model using low-TF mice and suggest that SMC-derived medial TF but not circulating TF may be critical for thrombosis in large arteries under conditions associated with endothelial denudation and exposure of the underlying SMC, such as those produced by human percutaneous coronary interventions. In contrast, circulating TF may contribute importantly to microvascular thrombosis, such as that produced by laser injury. Additional experiments will be needed in a wider array of models to better establish the relative contributions of SMCderived arterial wall TF and circulating TF to intravascular thrombosis. SMC-derived TF and the response to arterial injury Studies using inhibitors of TF activity, such as inactivated factor VIIa, TFPI or TF antibodies, have provided evidence that TF plays a key role in mediating intimal hyperplasia and luminal narrowing in response to arterial injury in mouse, rat, rabbit, and porcine models (reviewed in [6]). Low-TF mice also displayed a marked reduction in intimal hyperplasia in response to femoral artery injury [17]. SMC-specific TF-deficient mice have a similar reduction (~60%) in I/M ratio in response to arterial injury, suggesting that TF present in the SMC of the arterial wall, rather than from circulating sources, may be largely responsible for TF-mediated regulation of intimal hyperplasia [Wang L, Mackman N, Taubman MB, unpublished observations]. Many models of arterial injury are associated with little or no thrombus formation (particularly those involving rodents). This raises the question as to whether TF mediates changes in the arterial wall independent of its role in thrombosis. A number of studies have suggested
S80 that TF mediates migration of SMC or fibroblasts. Factor VIIa enhances PDGF-mediated migration of cultured fibroblasts [18] and induces migration of mouse SMC, whereas isolated TF:VIIa complexes induce SMC migration [19]. SMC derived from low-TF mice had a 71% decrease in migration in a modified Boyden chamber in response to 10% fetal bovine serum. The precise mechanism by which TF mediates SMC migration remains to be determined. Because TF has a transmembrane-spanning domain and a cytoplasmic tail, it has the potential to be involved in transmembrane signaling. This could in part explain the effects of TF inhibition on intimal hyperplasia. The cytoplasmic domain of TF interacts with actin binding protein 280 to mediate cytoskeletal arrangement and cell spreading [20]. The cytoplasmic domain has also been implicated in tumor metastasis (reviewed in [21]), although the mechanism remains to be determined. Products of TF-dependent activation of the coagulation cascade have direct cellular effects. Thrombin regulates growth, migration, and the synthesis of inflammatory mediators and receptors in SMC, and has been implicated in the progression of atherosclerosis and in the response to arterial injury (reviewed in [22]). Factor VIIa induces a variety of intracellular signals associated with cell growth and migration, including mobilization of intracellular Ca2+ , activation of phospholipase C, and induction of mitogenactivated protein (MAP) and Src kinases. Many of these effects are dependent upon TF, but independent of its cytoplasmic domain [23,24]. Protease activated receptor (PAR)2 has been implicated in VIIa-mediated cell activation [25], as has a receptor distinct from the PARs [26]. Factor Xa has also been implicated in cell proliferation and induces signals associated with proliferation and migration, similar to those described above (referenced in [27]). Summary In summary, current data suggest that SMCderived TF is likely to play a critical role in mediating arterial thrombosis and the intimal response to arterial injury. In addition, SMC are a major source of TF in atherosclerotic plaques and are thus likely to be involved in mediating thrombosis associated with plaque rupture. The availability of new animal models should allow for a more precise definition of the relative contribution of SMC-derived TF and circulating TF to these processes. Local inhibition of SMCderived arterial TF may be worth considering as
M.B. Taubman et al. a novel approach to inhibiting intimal hyperplasia and thrombosis associated with percutaneous vascular interventions. Conflict of interest statement None of the authors have a conflict of interest. References [1] Nemerson Y. Tissue factor: then and now. Thromb Haemost 1995;74(1):180 4. [2] Mackman N. Role of tissue factor in hemostasis and thrombosis. Blood Cells Mol Dis 2006;36(2):104 7. [3] Taubman MB. Tissue factor regulation in vascular smooth muscle: a summary of studies performed using in vivo and in vitro models. Am J Cardiol 1993;72(8):55C 60C. [4] Schecter AD, Berman AB, Taubman MB. Chemokine receptors in vascular smooth muscle. Microcirculation 2003;10(3 4):265 72. [5] Schecter AD, Spirn B, Rossikhina M, Giesen PL, Bogdanov V, Fallon JT, et al. Release of active tissue factor by human arterial smooth muscle cells. Circ Res 2000;87(2): 126 32. [6] Taubman MB, Giesen PL, Schecter AD, Nemerson Y. Regulation of the procoagulant response to arterial injury. Thromb Haemost 1999;82(2):801 5. [7] Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1989;86(8):2839 43. [8] Jang IK, Gold HK, Leinbach RC, Fallon JT, Collen D, Wilcox JN. Antithrombotic effect of a monoclonal antibody against tissue factor in a rabbit model of platelet-mediated arterial thrombosis. Arterioscler Thromb 1992;12(8):948 54. [9] Pawashe AB, Golino P, Ambrosio G, Migliaccio F, Ragni M, Pascucci I, et al. A monoclonal antibody against rabbit tissue factor inhibits thrombus formation in stenotic injured rabbit carotid arteries. Circ Res 1994;74(1):56 63. [10] Golino P, Ragni M, Cirillo P, D’Andrea D, Scognamiglio A, Ravera A, et al. Antithrombotic effects of recombinant human, active site-blocked factor VIIa in a rabbit model of recurrent arterial thrombosis. Circ Res 1998;82(1):39 46. [11] Asada Y, Hara S, Tsuneyoshi A, Hatakeyama K, Kisanuki A, Marutsuka K, et al. Fibrin-rich and plateletrich thrombus formation on neointima: recombinant tissue factor pathway inhibitor prevents fibrin formation and neointimal development following repeated balloon injury of rabbit aorta. Thromb Haemost 1998;80(3): 506 11. [12] Roque M, Reis ED, Fuster V, Padurean A, Fallon JT, Taubman MB, et al. Inhibition of tissue factor reduces thrombus formation and intimal hyperplasia after porcine coronary angioplasty. J Am Coll Cardiol 2000;36(7):2303 10. [13] Chou J, Mackman N, Merrill-Skoloff G, Pedersen B, Furie BC, Furie B. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004;104(10):3190 7. [14] Giesen PL, Rauch U, Bohrmann B, Kling D, Roque M, Fallon JT, et al. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 1999;96(5):2311 5. [15] Butenas S, Mann KG. Active tissue factor in blood? Nat Med 2004;10(11):1155 6; author reply 1156.
The role of smooth muscle derived tissue factor in mediating thrombosis and arterial injury [16] Day SM, Reeve JL, Pedersen B, Farris DM, Myers DD, Im M, et al. Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall. Blood 2005; 105(1):192 8. [17] Pyo R, Jensen KK, Wiekowski MT, Manfra D, Alcami A, Taubman MB, et al. Inhibition of intimal hyperplasia in transgenic mice conditionally expressing the chemokinebinding protein M3. Am J Pathol 2004;164(6):2289 97. [18] Siegbahn A, Johnell M, Rorsman C, Ezban M, Heldin CH, Ronnstrand L. Binding of factor VIIa to tissue factor on human fibroblasts leads to activation of phospholipase C and enhanced PDGF-BB-stimulated chemotaxis. Blood 2000;96(10):3452 8. [19] Sato Y, Asada Y, Marutsuka K, Hatakeyama K, Kamikubo Y, Sumiyoshi A. Tissue factor pathway inhibitor inhibits aortic smooth muscle cell migration induced by tissue factor/factor VIIa complex. Thromb Haemost 1997;78(3): 1138 41. [20] Ruf W. Tissue factor-dependent signaling in tumor biology. Pathophysiol Haemost Thromb 2003;33(Suppl 1):28 30. [21] Belting M, Ahamed J, Ruf W. Signaling of the tissue factor coagulation pathway in angiogenesis and cancer. Arterioscler Thromb Vasc Biol 2005;25(8):1545 50.
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[22] Patterson C, Stouffer GA, Madamanchi N, Runge MS. New tricks for old dogs: nonthrombotic effects of thrombin in vessel wall biology. Circ Res 2001;88(10):987 97. [23] Camerer E, Rottingen JA, Gjernes E, Larsen K, Skartlien AH, Iversen JG, et al. Coagulation factors VIIa and Xa induce cell signaling leading to up-regulation of the egr-1 gene. J Biol Chem 1999;274(45):32225 33. [24] Petersen LC, Freskgard P, Ezban M. Tissue factordependent factor VIIa signaling. Trends Cardiovasc Med 2000;10(2):47 52. [25] Camerer E, Huang W, Coughlin SR. Tissue factorand factor X-dependent activation of protease-activated receptor 2 by factor VIIa. Proc Natl Acad Sci USA 2000;97(10):5255 60. [26] Petersen LC, Thastrup O, Hagel G, Sorensen BB, Freskgard PO, Rao LV, et al. Exclusion of known protease-activated receptors in factor VIIa-induced signal transduction. Thromb Haemost 2000;83(4):571 6. [27] McLean K, Schirm S, Johns A, Morser J, Light DR. FXainduced responses in vascular wall cells are PAR-mediated and inhibited by ZK-807834. Thromb Res 2001;103(4): 281 97.