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Updated: Dec 14, 2025
Author Spotlight: High-Sensitivity Tissue Factor Activity Assay for Plasma Diagnosis
Published on: December 29, 2023
Tissue factor in atherosclerosis and atherothrombosis
Steven P Grover1, Nigel Mackman1
1UNC Blood Research Center, Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Insights
Tissue factor (TF) drives blood clot formation in atherosclerosis, a chronic inflammatory disease. TF pathway inhibitor 1 (TFPI-1) modulates this process, impacting cardiovascular events like heart attack and stroke.
Area of Science:
- Cardiovascular Biology
- Hemostasis and Thrombosis
- Pathology
Background:
- Atherosclerosis is a chronic inflammatory arterial disease characterized by lipid-rich plaques.
- Atherothrombosis, the terminal stage, involves plaque rupture leading to occlusive thrombi, causing myocardial infarction and stroke.
- Tissue factor (TF) initiates coagulation via the TF:factor VIIa complex, crucial for arterial thrombosis in atherosclerosis.
Purpose of the Study:
- To review the role of TF-dependent coagulation activation in atherothrombotic disease.
- To highlight the significance of TF and its inhibitor, TFPI-1, in atherosclerotic plaques.
Main Methods:
- Literature review focusing on the contribution of TF to atherothrombosis.
- Analysis of studies investigating TF and TFPI-1 expression and function in atherosclerotic models.
Main Results:
- TF is highly expressed in atherosclerotic plaques by foam cells, smooth muscle cells, and extracellular vesicles.
- TF-mediated coagulation activation is critical for arterial thrombosis in atherosclerosis.
- TF pathway inhibitor 1 (TFPI-1) is present in plaques, and its modulation affects atherosclerosis in mouse models.
Conclusions:
- TF-dependent coagulation plays a pivotal role in the pathogenesis of atherothrombotic disease.
- Targeting TF or TFPI-1 may offer therapeutic strategies for atherosclerosis and its thrombotic complications.
Abstract:
Atherosclerosis is a chronic inflammatory disease that is characterized by the formation of lipid rich plaques in the wall of medium to large sized arteries. Atherothrombosis represents the terminal manifestation of this pathology in which atherosclerotic plaque rupture or erosion triggers the formation of occlusive thrombi. Occlusion of arteries and resultant tissue ischemia in the heart and brain causes myocardial infarction and stroke, respectively. Tissue factor (TF) is the receptor for the coagulation protease factor VIIa, and formation of the TF:factor VIIa complex triggers blood coagulation. TF is expressed at high levels in atherosclerotic plaques by both macrophage-derived foam cells and vascular smooth muscle cells, as well as extracellular vesicles derived from these cells. Importantly, TF mediated activation of coagulation is critically important for arterial thrombosis in the setting of atherosclerotic disease. The major endogenous inhibitor of the TF:factor VIIa complex is TF pathway inhibitor 1 (TFPI-1), which is also present in atherosclerotic plaques. In mouse models, increased or decreased expression of TFPI-1 has been found to alter atherosclerosis. This review highlights the contribution of TF-dependent activation of coagulation to atherthrombotic disease.
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