Tissue Factor and Atherothrombosis

Abstract

Tissue factor (TF) is known to be the key element in the initiation of the extrinsic pathway of the coagulation cascade and appears to be a critical determinant of atherosclerotic plaque thrombogenicity. TF is needed to produce thrombin from prothrombin. In the extrinsic pathway, TF activates factor Vll. TF is expressed mainly on subendothelial tissues, but TF expression may be induced on endothelial cells by inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha). Subendothelial TF is responsible for initiating fibrin formation at sites of vascular injury, bloodborne TF may be an important contributor to propagation of the developing thrombus. It has been postulated that the blood-borne TF initiates the thrombogenic stimulus, leading to the formation of larger and more stable thrombus. TF may attach to cellular receptors, which in turn affect the production and release of inflammatory mediators. Baseline plasma TF activity has been demonstrated as an independent predictor for cardiovascular death in patients with acute myocardial infarction. TF is expressed by macrophage-derived foam cells in atherosclerotic plaques. TF levels were higher in atheroma from patients with unstable angina than with stable angina. These results suggest that high levels of TF exposed upon plaque rupture trigger atherothrombosis. Inhibition of TF would be expected to reduce thrombosis associated with a variety of diseases. TF pathway is a potential target for new therapeutic agents that can decrease TF activity, such as active site-inactivated factor VIIa, recombinant TF inhibitor and antibodies against TF or peptides interfering with TF-FVIIa complex activity. Significant clinical forms of atherosclerosis, such as sudden death, myocardial infarction, and stroke have common pathogenesis. The occlusion of the vessel lumen is the result from atherosclerotic plaque rupture/erosion that initiate thrombus formation. This thrombus has complex structure and contains predominantly fibrin in addition to platelets, suggesting an important role for the coagulation cascade in plaque thrombus formation. Tissue factor (TF) is known to be the key element in the initiation of the extrinsic pathway of the coagulation cascade and appears to be a critical determinant of atherosclerotic plaque thrombogenicity.

The Nutraceutical Dehydrozingerone and Its Dimer Counteract Inflammation- and Oxidative Stress-Induced Dysfunction ofIn VitroCultured Human Endothelial Cells: A Novel Perspective for the Prevention and Therapy of Atherosclerosis

“…Functional changes of ECs also comprise an increased procoagulant activity [2], mediated by the induction of tissue factor (TF) on endothelial cells. TF is known to be the key element in the initiation of the coagulation cascade and appears to be a critical determinant of atherosclerotic plaque thrombogenicity [7]. TF is expressed mainly on subendothelial tissues, but its expression may be induced on endothelial cells by inflammatory mediators such as TNF- α .…”

“…TF is expressed mainly on subendothelial tissues, but its expression may be induced on endothelial cells by inflammatory mediators such as TNF- α . Subendothelial TF is responsible for initiating fibrin formation at sites of vascular injury whereas blood-born TF triggers atherothrombosis [7]. Due to the central role of endothelial dysfunction in atherosclerotic plaque formation and progression, the identification of novel medicinal agents able to counteract pathological functional changes of ECs is an important goal to reduce the severity of inflammation and to prevent atherosclerotic plaque development and thrombogenicity.…”

L162v Polymorphism of Par-Α Gene, A603g Polymorphism of Tissue Factor Gene and Risk of Coronary Heart Disease in Russian Population

“…In the case of activation of immune inflammation in the vessel wall the endothelial damage occur. The result is the release into the bloodstream of a large amount of tissue factor and start the coagulation cascade [24,25].…”

Therapeutic Antibody-Like Immunoconjugates against Tissue Factor with the Potential to Treat Angiogenesis-Dependent as Well as Macrophage-Associated Human Diseases

“…Interestingly, over 90% of microvesicles within plaques are CD14 positive [131], suggesting their origin of monocyte/macrophage. Several groups [132,133,134,135] have reviewed and linked TF to atherothrombosis and atherosclerosis. Animal models of atherosclerosis have been developed in mice, rabbits, swine and non-human primates, of which mice and rabbits are the most commonly used models.…”