Tissue Factor Is Induced by Monocyte Chemoattractant Protein-1 in Human Aortic Smooth Muscle and THP-1 Cells

Schecter, Alison D.; Rollins, Barrett J.; Zhang, Yujun J.; Charo, Israel F.; Fallon, John T.; Rossikhina, Maria; Giesen, Peter; Nemerson, Yale; Taubman, Mark B.

doi:10.1074/jbc.272.45.28568

Cited by 214 publications

(164 citation statements)

References 64 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…32 MCP-1 increases tissue factor expression and activity in human vascular smooth muscle cells. 33 We recently reported that 7ND gene transfer inhibited progression and destabilization of advanced atheroma by reducing inflammation in apoE-KO mice that were not received AngII. 24 We demonstrate the preservation of interstitial collagen in the atherosclerotic plaque associated with decreased expression of MMP and tissue factor by 7ND gene transfer.…”

Section: Discussionmentioning

confidence: 99%

Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice

Kitamoto

Ishibashi

et al. 2004

ATVB

100

View full text Add to dashboard Cite

Objective-Chronic inflammatory processes might be involved in the progression and destabilization of atherosclerotic plaques. Therefore, identification of the mechanism underlying arterial inflammatory function might lead to the development of novel therapeutic strategies. Angiotensin II (AngII) is implicated in atherogenesis by activating the vascular inflammation system, mainly through monocyte chemotaxis. Therefore, we hypothesized that AngII increases plaque size and promotes destabilization of established atheromas by activating the monocyte chemoattractant protein-1 (MCP-1) pathway. Methods and Results-We report here that 4-week infusion of AngII not only increased plaque size but also induced a destabilization phenotype (ie, increased macrophages and lipids and decreased collagen and smooth muscle cells) of pre-existing atherosclerotic lesions of hypercholesterolemic mice. AngII also enhanced the gene expression of inflammatory cytokines (TNF␣, etc.) and chemokines CCR2, etc Key Words: atherosclerosis Ⅲ hypercholesterolemia Ⅲ cell adhesion molecules Ⅲ inflammation Ⅲ gene therapy A therosclerosis and its complications are the major cause of death in Western countries. Recent evidence suggests that chronic inflammatory processes have an important role in atherosclerotic plaque progression, destabilization, and subsequent rupture/thrombosis, resulting in acute coronary syndrome and stroke. 1 Therefore, identification of the critical inflammatory pathway involved in plaque progression and destabilization of pre-existing established atheromas might aid in the development of novel therapeutic strategies to reduce atherothrombotic complications. Angiotensin II (AngII) is implicated in atherogenesis beyond its hemodynamic effects. 2 Infusion of AngII into hypercholesterolemic mice dramatically accelerates the development and/or progression of atherosclerotic lesions and the effects of AngII occurred independent of changes in arterial pressure or plasma lipid concentration. 3,4 The mechanism of AngII-induced enhancement of atherogenesis is probably multifactorial, and includes hemodynamic effects, endothelial dysfunction and activation, 5 oxidative stress, 6 and inflammation. 7,8 AngII increases monocyte chemotaxis, activates nuclear factor-B, and augments production of inflammatory cytokines and chemokines by arterial wall cells and monocytes. 9 -12 AngII is very important in the pathogenesis of atherothrombotic complications, as evidenced by clinical benefits of angiotensinconverting enzyme inhibition 13 and AngII receptor blockers. 14 There are no reports, however, that address the mechanism of AngII-induced enhancement of atherogenesis and plaque destabilization under in vivo conditions.Emerging evidence suggests that AngII activates cell inflammatory systems in arterial lesion. 1,2 Inflammatory changes in arterial lesions are characterized by the recruitment and activation of monocytes/macrophages, which are regulated by monocyte chemoattractant protein-1 (MCP-1). 15 Expression Vector7ND was constructed b...

show abstract

Section: Discussionmentioning

confidence: 99%

Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice

Kitamoto

Ishibashi

et al. 2004

ATVB

100

View full text Add to dashboard Cite

show abstract

“…Thus it is possible that endothelial production of JE/ MCP-1 draws in macrophages and serves as a cofactor in their activation and retention. JE/MCP-1 produced by hypoxic endothelium could also have an integral role in increased expression of tissue factor levels observed in smooth muscle cells 39,40 in hypoxemic vasculature. Aside from these questions of the basic biology of the procoagulant response, recognition of the relative vulnerability of the lung to hypoxemia-associated fibrin deposition in the mouse may also provide important insights.…”

Section: Conclusion/hypothesismentioning

confidence: 99%

Hypoxia/Hypoxemia-Induced Activation of the Procoagulant Pathways and the Pathogenesis of Ischemia-Associated Thrombosis

Yan

Mackman

Kisiel

et al. 1999

ATVB

167

View full text Add to dashboard Cite

Abstract-Although oxygen deprivation has long been associated with triggering of the procoagulant pathway and venous thrombosis, blood hypoxemia and stasis by themselves do not lead to fibrin formation. A pathway is outlined through which diminished levels of oxygen activate the transcription factor early growth response-1 (Egr-1) leading to de novo transcription/translation of tissue factor in mononuclear phagocytes and smooth muscle cells, which eventuates in vascular fibrin deposition. The procoagulant response is magnified by concomitant suppression of fibrinolysis by hypoxia-mediated upregulation of plasminogen activator inhibitor-1. These data add a new facet to the biology of thrombosis associated with hypoxemia/stasis and imply that interference with mechanisms causing Egr-1 activation in response to oxygen deprivation might prevent vascular fibrin deposition occurring in ischemia without directly interfering with other pro/anticoagulant pathways. Key Words: tissue factor Ⅲ hypoxia Ⅲ ischemia Ⅲ Egr-1 Ⅲ PAI-1 I n the 1850s, Virchow described the association between venous thrombosis and a triad of contributing factors, including hypercoagulability, vascular damage, and vascular stasis. 1 More recently, venous stasis has been linked to the rapid decline in intravascular oxygen tension and thrombus formation in veins of the lower extremities. [2][3][4] Definition of mechanisms through which low levels of oxygen cause blood to clot has been more elusive. The Wessler stasis model of venous thrombosis, 5,6 in which a rabbit vascular segment (typically the jugular vein) is occluded and a fibrin clot subsequently forms after addition of a procoagulant, demonstrated that acute lack of blood flow and/or hypoxemia, although necessary, were not sufficient, at least acutely, to trigger clot formation. Without inclusion of a strong procoagulant stimulus, such as activated clotting factors (eg, Factors IXa, Xa, or thrombin), fibrin deposition did not occur. These observations have been extended to different types of vessels, and this has led to the same conclusion; acute occlusion of normal vessels with their normal blood content does not by itself promote fibrin formation. This situation must be differentiated from that of an atherosclerotic or other pathologic vessel, in which abundant neointimal tissue factor, a maximal prothrombotic stimulus, is immediately exposed to blood contents, triggering rapid coagulation. In fact, the intact, healthy vessel wall has very low levels of tissue factor with an increasing gradient toward the adventitia. The cell type most uniformly accepted as being capable of expressing substantive amounts of tissue factor within the intravascular space in response to environmental stimuli is the mononuclear phagocyte, although polymorphonuclear leukocytes may also contribute, and endothelial cells have been shown to produce tissue factor in selected settings. 7,8 Thus it may not be surprising that a brief period of hypoxemia and/or stasis alone in a normal vessel are not sufficient to trigger ...

show abstract

“…In SMC, serum and various other agonists, including thrombin, platelet-derived growth factor, angiotensin II, and monocyte chemoattractant protein-1, have been shown to induce TF expression in vitro (15,16). We have recently observed that low density lipoprotein (LDL), the levels of which correlate with vascular disease, enhance TF mRNA and TF surface protein in human and rat SMC (17).…”

mentioning

confidence: 99%

Native and Oxidized Low Density Lipoprotein Induction of Tissue Factor Gene Expression in Smooth Muscle Cells Is Mediated by Both Egr-1 and Sp1

Cui¹,

Penn

Chisolm

1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

Tissue factor, in association with factor VIIa, initiates the coagulation cascade. We studied the influences of two pathophysiological stimuli, native (unmodified) and oxidized low density lipoprotein, on tissue factor gene expression in a cell important in vascular remodeling and vascular diseases, the smooth muscle cell. Our results demonstrated that both lipoproteins significantly induced tissue factor gene expression in rat aortic smooth muscle cells; oxidized low density lipoprotein was slightly more potent. Both lipoproteins increased tissue factor mRNA in a concentration-and time-dependent manner. Results from nuclear run-on assays and mRNA stability experiments indicated that increased tissue factor mRNA accumulation in response to the lipoproteins was principally controlled at the transcriptional level. By using lipid extracts of low density lipoprotein or methylation of the intact lipoprotein to block receptor recognition, we showed that this lipoprotein induced tissue factor mRNA via both receptor-independent and receptor-augmented pathways. Transfection studies using a series of deleted tissue factor promoters revealed that a ؊143-to ؉106-base pair region of the rat tissue factor promoter contained regulatory elements required for lipoprotein-mediated induction. Electrophoretic mobility shift assays showed that the binding activities of the transcription factor Egr-1, but not Sp1, were markedly elevated in response to these lipoproteins. Transfection of site-directed mutants of the tissue factor (TF) promoter demonstrated that not only Egr-1 but also Sp1 cis-acting elements in the TF (؊143) promoter construct were necessary for optimal TF gene induction. Our data show for the first time that both low density lipoprotein and oxidized low density lipoprotein induce tissue factor gene expression in smooth muscle cells and that this tissue factor gene expression is mediated by both Egr-1 and Sp1 transcription factors.Tissue factor (TF) 1 expression within the vasculature can activate the coagulation protease cascade and promote thrombotic episodes in a variety of disorders, including cancer, atherosclerosis, and septic shock (reviewed in Refs. 1-3). In atherosclerotic plaques, enhanced TF expression has been detected in association with smooth muscle cells (SMC), macrophages, the lipid-rich necrotic core, and the endothelium overlying the plaque (4 -7). It is important to understand how TF is regulated in SMC, since TF in advancing lesions could exacerbate coagulation after injury, promote SMC proliferation via thrombin generation (8), and reduce atherosclerotic plaque stability.In monocytic cells, endothelial cells, and epithelial cells, TF gene induction by tumor necrosis factor-␣ (TNF-␣), lipopolysaccharide (LPS), phorbol ester (phorbol 12-myristate 13-acetate), and serum is well documented (9 -14). In SMC, serum and various other agonists, including thrombin, platelet-derived growth factor, angiotensin II, and monocyte chemoattractant protein-1, have been shown to induce TF expression in vitro (15,16...

show abstract

Tissue Factor Is Induced by Monocyte Chemoattractant Protein-1 in Human Aortic Smooth Muscle and THP-1 Cells

Cited by 214 publications

References 64 publications

Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice

Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice

Hypoxia/Hypoxemia-Induced Activation of the Procoagulant Pathways and the Pathogenesis of Ischemia-Associated Thrombosis

Native and Oxidized Low Density Lipoprotein Induction of Tissue Factor Gene Expression in Smooth Muscle Cells Is Mediated by Both Egr-1 and Sp1

Contact Info

Product

Resources

About