Characterization of a tissue factor/factor VIIa‐dependent model of thrombosis in hypercholesterolemic rabbits

L, Chi; Gibson, Glenn; Yw, Peng; Bousley, Richard F.; Brammer, David W.; Rekhter, Mark D.; Chen, J; Leadley, Robert J.

doi:10.1111/j.1538-7836.2004.00547.x

Cited by 23 publications

(15 citation statements)

References 25 publications

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“…115,116 Although murine models do not typically display spontaneous atherothrombosis, intravital models of arterial thrombosis address thrombus formation in macrovascular beds in the context of activated or damaged endothelium. Vessel wall TF is unequivocally involved in thrombus initiation in arterial thrombosis, 117 however, the role of circulating leukocyte or leukocyte-derived TF regulating arterial thrombus formation is less clear. The inhibition of leukocyte accumulation using an anti-P-selectin antibody in a baboon model of arterial thrombus significantly attenuated fibrin formation and decreased thrombus stability.…”

Section: Leukocytes Contribute To Arterial Thrombosismentioning

confidence: 99%

The role of leukocytes in thrombosis

Swystun

Liaw

2016

Blood

243

184

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In recent years, the traditional view of the hemostatic system as being regulated by a coagulation factor cascade coupled with platelet activation has been increasingly challenged by new evidence that activation of the immune system strongly influences blood coagulation and pathological thrombus formation. Leukocytes can be induced to express tissue factor and release proinflammatory and procoagulant molecules such as granular enzymes, cytokines, and damage-associated molecular patterns. These mediators can influence all aspects of thrombus formation, including platelet activation and adhesion, and activation of the intrinsic and extrinsic coagulation pathways. Leukocyte-released procoagulant mediators increase systemic thrombogenicity, and leukocytes are actively recruited to the site of thrombus formation through interactions with platelets and endothelial cell adhesion molecules. Additionally, phagocytic leukocytes are involved in fibrinolysis and thrombus resolution, and can regulate clearance of platelets and coagulation factors. Dysregulated activation of leukocyte innate immune functions thus plays a role in pathological thrombus formation. Modulation of the interactions between leukocytes or leukocyte-derived procoagulant materials and the traditional hemostatic system is an attractive target for the development of novel antithrombotic strategies.

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Section: Leukocytes Contribute To Arterial Thrombosismentioning

confidence: 99%

The role of leukocytes in thrombosis

Swystun

Liaw

2016

Blood

243

184

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“…In one study, disruption of the atherosclerotic plaques induced thrombosis, which was inhibited by active-site inhibited FVIIa. 86 Another study showed that arterial thrombosis was reduced by administration of TFPI. 87 We investigated the role of vessel wall TF in a mouse carotid arterial thrombosis model that involves acute oxidative damage of the vessel wall and denudation of the endothelium.…”

Section: Relative Contribution Of Vessel Wall Tf and Mp Tf To Arteriamentioning

confidence: 99%

“…93 In a rabbit model, balloon catheter-induced endothelial denudation of the aorta or femoral artery increased TF expression in the vessel wall. 86,94 Therefore, damage of normal or diseased arteries would expose TF to blood leading to the formation of an occlusive thrombus ( Figure 3). In one study, disruption of the atherosclerotic plaques induced thrombosis, which was inhibited by active-site inhibited FVIIa.…”

Section: Relative Contribution Of Vessel Wall Tf and Mp Tf To Arteriamentioning

confidence: 99%

Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis

Mackman

Tilley

Key

2007

ATVB

583

441

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Abstract-Hemostasis requires both platelets and the coagulation system. At sites of vessel injury, bleeding is minimized by the formation of a hemostatic plug consisting of platelets and fibrin. The traditional view of the regulation of blood coagulation is that the initiation phase is triggered by the extrinsic pathway, whereas amplification requires the intrinsic pathway. The extrinsic pathway consists of the transmembrane receptor tissue factor (TF) and plasma factor VII/VIIa (FVII/FVIIa), and the intrinsic pathway consists of plasma FXI, FIX, and FVIII. Under physiological conditions, TF is constitutively expressed by adventitial cells surrounding blood vessels and initiates clotting. In addition so-called blood-borne TF in the form of cell-derived microparticles (MPs) and TF expression within platelets suggests that TF may play a role in the amplification phase of the coagulation cascade. Under pathologic conditions, TF is expressed by monocytes, neutrophils, endothelial cells, and platelets, which results in an elevation of the levels of circulating TF-positive MPs. TF expression within the vasculature likely contributes to thrombosis in a variety of diseases. Understanding how the extrinsic pathway of blood coagulation contributes to hemostasis and thrombosis may lead to the development of safe and effective hemostatic agents and antithrombotic drugs. Key Words: coagulation Ⅲ arterial thrombosis Ⅲ deep vein thrombosis T he hemostatic system maintains blood in a fluid state under normal conditions and responds to vessel injury by the rapid formation of a clot. Disruption of the endothelium exposes platelets to collagen in the vessel wall and plasma factor VII/VIIa (FVII/FVIIa) to extravascular tissue factor (TF; Figure 1). Other proteins, such as von Willebrand factor (vWF), facilitate the binding of platelets to the injured vessel wall. The TF:FVIIa complex is traditionally referred to as the extrinsic pathway and is proposed to be the primary activator of the coagulation protease cascade in vivo. Subsequently, propagation of the thrombus involves recruitment of additional platelets and amplification of the coagulation cascade by the intrinsic pathway of blood coagulation, which includes the hemophilia factors FVIII and FIX (Figure 1). Importantly, platelets play a critical role in the amplification of the coagulation cascade by providing a thrombogenic surface. Finally, fibrin stabilizes the platelet-rich thrombus (Figure 1). This review focuses on the role of the extrinsic pathway (TF and FVIIa) in hemostasis and thrombosis. See cover TF and FVII in HemostasisHemostasis is the protective physiological response to vascular injury that results in exposure of blood components to the subendothelial layers of the vessel wall. TF is constitutively expressed by certain cells within the vessel wall and cells surrounding blood vessels, such as vascular smooth muscle cells, pericytes, and adventitial fibroblasts. 1-5 TF is also expressed in a tissue-specific pattern with high levels in the brain, lung, kidney, he...

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“…In line with this, disruption of atherosclerotic plaques leads to exposure of TF to the blood resulting in formation of an occlusive thrombus (Figure 6), and active-site inhibited FVIIa inhibits thrombus formation on top of a ruptured plaque supporting the role of vessel-wall TF in arterial thrombosis. 87 In venous thrombosis, stasis of the blood stream is more important to induce thrombosis than vessel damage; thus, circulating TF should play a crucial role under these conditions. Indeed, in a jugular vein model using collagen-coated cotton thread, inhibition of TF reduced thrombosis even without endothelial injury.…”

Section: Tf and Thrombosismentioning

confidence: 99%

Tissue Factor and Cardiovascular Disease: Quo Vadis?

Berndt

Tanner

Lüscher

2010

Circ J

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The coagulation cascade represents a system of proteases responsible to maintain vascular integrity and to induce rapid clot formation after vessel injury. Tissue factor (TF), the key initiator of the coagulation cascade, binds to factor VIIa and thereby activates factor IX and factor X, resulting in thrombus formation. Different stimuli enhance TF gene expression in endothelial and vascular smooth muscle cells. In addition to these vascular cells, TF has recently been detected in the bloodstream in circulating cells such as leukocytes and platelets, as a component of microparticles, and as a soluble, alternatively spliced form of TF. Various cardiovascular risk factors like hypertension, diabetes, and dyslipidemia, increase levels of TF. In line with this observation, enhanced vascular TF expression occurs during atherogenesis, particularly in patients with acute coronary syndromes. (Circ J 2010; 74: 3 - 12)

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Characterization of a tissue factor/factor VIIa‐dependent model of thrombosis in hypercholesterolemic rabbits

Cited by 23 publications

References 25 publications

The role of leukocytes in thrombosis

The role of leukocytes in thrombosis

Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis

Tissue Factor and Cardiovascular Disease: Quo Vadis?

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