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.


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.
Tilley
Rachel E
RE
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Pedersen
Brian
B
Pawlinski
Rafal
R
Sato
Yuichiro
Y
Erlich
Jonathan H
JH
Shen
Yuechun
Y
Day
Sharlene
S
Huang
Ying
Y
Eitzman
Daniel T
DT
Boisvert
William A
WA
Curtiss
Linda K
LK
Fay
William P
WP
Mackman
Nigel
N
D000818:Animals; D001011:Aorta / Q000473:pathology / Q000502:physiology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D016026:Bone Marrow Transplantation; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011973:Receptors, LDL / Q000235:genetics; D013925:Thromboplastin / Q000235:genetics* / Q000378:metabolism*
D001057:Apolipoproteins E; D011973:Receptors, LDL; D013925:Thromboplastin