Atherosclerosis in Mice Is Not Affected by a Reduction in Tissue Factor Expression

OBJECTIVE—To determine whether tissue factor (TF) contributes to the progression of atherosclerotic lesions in mice. METHODS AND RESULTS—We determined the effect of a 50% reduction of TF levels in all cells on atherosclerosis in apolipoprotein E-deficient (apoE) mice. No differences were observed in the extent of atherosclerosis in apoE/TF and apoE/TF mice fed regular chow for 34 weeks. Atherosclerosis could not be analyzed in apoE mice expressing low levels of TF because of premature death of these mice. Macrophages are a major source of TF in atherosclerotic plaques. Therefore, in a second series of experiments, we investigated the effect on atherosclerosis of selectively reducing hematopoietic cell-derived TF by transplanting bone marrow from mice expressing low levels of TF into low-density lipoprotein receptor deficient (LDLR) mice. Atherosclerosis within the arterial tree and aortic root were similar in LDLR mice with low-TF bone marrow compared with control bone marrow (TF or TF) after 4 and 16 weeks on an atherogenic diet. Furthermore, the cellular composition of the aortic root lesions was similar between the 2 groups. CONCLUSIONS—Our data indicate that either a 50% reduction of TF in all cells or a selective reduction in hematopoietic cell-derived TF does not affect the development of atherosclerotic lesions in mice.