Tissue factor in atherosclerosis (original) (raw)
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Physiological research / Academia Scientiarum Bohemoslovaca, 2008
Tissue factor is a cell surface protein that is expressed constitutively by monocytes, macrophages and fibroblasts, but also by some other cells in response to a variety of stimuli. The main function of the tissue factor is to form a complex with factor VII/VIIa that converts factors IX and X to their active forms. Tissue factor is also involved in the pathophysiology of systemic inflammatory disorders, coagulopathies, atherosclerotic disease, tumor angiogenesis and metastasis. Increased tissue factor expression either locally in the coronary plaques or systematically on circulating blood elements of patients with acute coronary syndromes may be responsible for increased thrombin generation, thus leading to platelet activation and fibrin formation. Tissue factor therefore plays a pivotal role in the initiation of thrombotic complications in patients with coronary artery disease.
Tissue Factor and Atherosclerosis: Not only vessel wall-derived TF, but also platelet-associated TF
2011
In the last ten years the contribution of both vessel wall-derived tissue factor (TF) and platelets to atherosclerosis has been revisited. At the beginning of the 2000 a circulating blood-borne TF has been proposed to sustain coagulation activation and propagation on the edge of a growing thrombus. Concomitantly with the observation that platelets not only contribute to thrombus formation, but also take part to the onset of the atherosclerotic lesion, evidences have been provided that they express functionally active TF, making them able to trigger the coagulation cascade.
Seminars in thrombosis and hemostasis, 2015
The contribution of vessel wall-derived tissue factor (TF) to atherothrombosis is well established, whereas the pathophysiological relevance of the blood-borne TF is still a matter of debate, and controversies on the presence of platelet-associated TF still exist. In the past 15 years, several studies have documented the presence of TF in human platelets, the capacity of human platelets to use TF mRNA to make de novo protein synthesis, and the increase in the percentage of TF positive platelets in pathological conditions such as coronary artery disease (CAD). The exposure of vessel wall-derived TF at the site of vascular injury would play its main role in the initiation phase, whereas the blood-borne TF carried by platelets would be involved in the propagation phase of thrombus formation. More recent data indicate that megakaryocytes are committed to release into the bloodstream a well-defined number of TF-carrying platelets, which represents only a fraction of the whole platelet po...
The role of tissue factor in thrombosis and hemostasis
Physiol Res, 2007
The tissue factor (TF) is one of the most important regulators of arterial thrombosis. Because arterial thrombosis is the pathophysiologic background of acute coronary syndrome, the possible impact of blocking the arterial thrombosis on its onset is a challenging problem. The investigations of TF brought a new concept of "cell-based coagulation model" which highlighted the question of blood-borne TF as a source of TF in circulating blood. In this review we summarize essential information on the pathophysiology, molecular structure, expression and distribution of TF and we propose a novel concept of blood-borne TF, suggesting the possibilities of inhibition of the coagulation cascade with newly synthetized drugs.
Tissue factor: newer concepts in thrombosis and its role beyond thrombosis and hemostasis
Cardiovascular Diagnosis and Therapy
For many years, the attention on tissue factor (TF) in human pathophysiology has been limited to its role as initiator of extrinsic coagulation pathway. Moreover, it was described as a glycoprotein located in several tissue including vascular wall and atherosclerotic plaque. However, in the last two decades, the discovery that TF circulates in the blood as cell-associated protein, microparticles (MPs) bound and as soluble form, is changing this old vessel-wall TF dogma. Moreover, it has been reported that TF is expressed by different cell types, even T lymphocytes and platelets, and different pathological conditions, such as acute and chronic inflammatory status, and cancer, may enhance its expression and activity. Thus, recent advances in the biology of TF have clearly indicated that beyond its known effects on blood coagulation, it is a "true surface receptor" involved in many intracellular signaling, cell-survival, gene and protein expression, proliferation, angiogenesis and tumor metastasis. Finally, therapeutic modulation of TF expression and/ or activity has been tested with controversial results. This report, starting from the old point of view about TF as initiator of extrinsic coagulation pathway, briefly illustrates the more recent concepts about TF and thrombosis and finally gives an overview about its role beyond thrombosis and haemostasis focusing on the different intracellular mechanisms triggered by its activation and potentially involved in atherosclerosis.