期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 51, 页码 17795-17800出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0408096101
关键词
animal models; genetics; innominate artery
资金
- NHLBI NIH HHS [HL-54591-08, P01 HL054591, HL70524-02, U01 HL070524] Funding Source: Medline
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 approximate to85% in fractalkine-deficient females [42,251 26,136 mum(2) (n = 15) vs. 6,538 11,320 mum(2); (n = 24), P < 0.0001] and males [36,911 +/- 32,504 mum(2) (n = 24) vs. 6,768 +/- 8,595 mum(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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