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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:555.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Rachel E. Tilley; Brian Pedersen; Rafal Pawlinski; Yuichiro Sato; Jonathan H. Erlich; Yuechun Shen; Sharlene Day; Ying Huang; Daniel T. Eitzman; William A. Boisvert; Linda K. Curtiss; William P. Fay; Nigel Mackman

From the Department of Immunology (R.E.T., B.P., R.P., Y.S., L.K.C., N.M.), The Scripps Research Institute, La Jolla, Calif; the Department of Cell Biology (N.M.), The Scripps Research Institute, La Jolla, Calif; University of New South Wales (J.H.E.), Sydney, Australia; the Department of Internal Medicine (Y.S., S.D., Y.H., D.T.E.), University of Michigan Medical School, Ann Arbor, Mich; the Department of Vascular Medicine Research (W.A.B.), Harvard Medical School, Cambridge, Mass; and the Department of Internal Medicine (W.P.F.), University of Missouri at Columbia, Mo.

Correspondence to Nigel Mackman, The Scripps Research Institute,10550 North Torrey Pines Road, CVN-18, La Jolla, CA 92037. E-mail nmackman{at}scripps.edu

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.

We sought to determine whether tissue factor (TF) contributes to the progression of atherosclerotic lesions in mice. A 50% reduction of TF in all cells or a selective reduction of TF in hematopoietic cells does not affect the development of atherosclerotic lesions in 2 mouse models. TF does not contribute to the progression of atherosclerosis in mice.

Key Words: atherosclerosis • macrophages • mice • tissue factor

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