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Atherosclerosis in mice is not affected by a reduction in tissue factor expression
Rachel E Tilley1, Brian Pedersen, Rafal Pawlinski
1Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Arteriosclerosis, Thrombosis, and Vascular Biology
|December 31, 2005
Summary
Reducing tissue factor (TF) in all cells or specifically in hematopoietic cells did not impact atherosclerotic lesion development in mouse models. These findings suggest TF may not be a critical driver of atherosclerosis progression.
Area of Science:
- Cardiovascular Biology
- Immunology
- Genetics
Background:
- Atherosclerosis is a chronic inflammatory disease characterized by plaque buildup in arteries.
- Tissue Factor (TF) is a procoagulant protein implicated in thrombosis and inflammation.
- The role of TF in atherosclerotic lesion progression remains incompletely understood.
Purpose of the Study:
- To investigate the contribution of Tissue Factor (TF) to the development and progression of atherosclerotic lesions.
- To determine if reducing TF levels in all cells affects atherosclerosis.
- To assess the impact of selectively reducing TF in hematopoietic cells on atherosclerosis.
Main Methods:
- Used apolipoprotein E-deficient (apoE(-/-)) mice with a 50% reduction in TF levels to study overall TF contribution.
- Utilized low-density lipoprotein receptor-deficient (LDLR(-/-)) mice transplanted with bone marrow from low-TF expressing mice to assess hematopoietic TF.
- Administered standard chow or atherogenic diets and analyzed atherosclerotic lesion extent and cellular composition.
Main Results:
- A 50% reduction in TF levels in all cells did not alter atherosclerosis in apoE(-/-) mice on regular chow.
- Selective reduction of TF in hematopoietic cells did not affect atherosclerosis development or lesion composition in LDLR(-/-) mice on an atherogenic diet.
- Premature death prevented analysis of atherosclerosis in apoE(-/-) mice with very low TF levels.
Conclusions:
- A 50% reduction in TF across all cells does not influence atherosclerotic lesion development in mice.
- Selective reduction of TF in hematopoietic cells does not impact the progression of atherosclerosis.
- These findings suggest that TF may not be a critical factor in the development of atherosclerotic lesions under these experimental conditions.