| Authors |
Teupser D, Pavlides S, Tan M, Gutierrez-Ramos JC, Kolbeck R, Breslow JL
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| Submitted By |
Jan Breslow on 2/23/2009 |
| Status |
Published |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Year |
2004 |
| Date Published |
12/21/2004 |
| Volume : Pages |
101(51) : 17795 - 17800 |
| PubMed Reference |
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| Abstract |
Fractalkine (CX3CL1) is of particular interest in atherogenesis because it can
serve as an adhesion molecule and a chemokine. Fractalkine and its receptor
CX3CR1 are expressed in atherosclerotic lesions of humans and mice. However, the
effect of fractalkine deficiency on atherosclerosis susceptibility is unknown.
Fractalkine-deficient mice on the C57BL/6 (B6) background were bred to the
atherosclerosis-sensitizing B6.ApoE(-/-) and B6.LDLR(-/-) backgrounds. Compared
with controls, aortic-root lesion area was unchanged in fractalkine-deficient
male and female B6.ApoE(-/-) mice at 16 weeks of age and males at 12 weeks of
age, but it was mildly reduced (30%, P = 0.005) in females at 12 weeks of age.
In contrast, lesion area at the brachiocephalic artery (BCA) was reduced
dramatically by approximately 85% in fractalkine-deficient females [42,251 +/-
26,136 microm(2) (n = 15) vs. 6,538 +/- 11,320 microm(2);(n = 24), P < 0.0001]
and males [36,911 +/- 32,504 microm(2) (n = 24) vs. 6,768 +/- 8,595 microm(2) (n
= 14); P = 0.001] at 16 weeks of age. Fractalkine-deficient B6.ApoE(-/-) mice
were comparable with controls in body weight, plasma cholesterol, plasma
high-density lipoprotein cholesterol and white blood cell counts. On the
B6.LDLR(-/-) background, lesion areas were reduced by 35% at the aortic root (P
< 0.01) and by 50% at the BCA (P < 0.05) in fractalkine-deficient females at 16
weeks of age. Lesions in fractalkine-deficient mice on the B6.ApoE(-/-) and
B6.LDLR(-/-) backgrounds were less complex and contained significantly fewer
macrophages than controls. In conclusion, the major reduction of atherosclerosis
in fractalkine-deficient mice appears to be at the BCA rather than the aortic
root.
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