| First Author | Combadière C | Year | 2003 |
| Journal | Circulation | Volume | 107 |
| Issue | 7 | Pages | 1009-16 |
| PubMed ID | 12600915 | Mgi Jnum | J:103047 |
| Mgi Id | MGI:3608391 | Doi | 10.1161/01.cir.0000057548.68243.42 |
| Citation | Combadiere C, et al. (2003) Decreased atherosclerotic lesion formation in CX3CR1/apolipoprotein E double knockout mice. Circulation 107(7):1009-16 |
| abstractText | BACKGROUND: Fractalkine (CX3CL1), a CX3C chemokine, is expressed in the vessel wall and mediates the firm adhesion and chemotaxis of leukocytes expressing its receptor, CX3CR1. A polymorphism in the CX3CR1 gene is associated with low CX3CR1 expression and reduced risk of acute coronary disease in humans. METHODS AND RESULTS: We generated CX3CR1-deficient mice (CX3CR1(-/-)) by targeted gene disruption and crossed them with the proatherogenic apolipoprotein E-deficient mice (apoE(-/-)). Here we show that the extent of lipid-stained lesions in the thoracic aorta was reduced by 59% in CX3CR1/apoE double knockout mice compared with their CX3CR1(+/+)/apoE(-/-) littermates. The development of atherosclerosis in the aortic sinus was also markedly altered in the double knockout mice, with 50% reduction in macrophage accumulation. Although lesions of CX3CR1(-/-) mice were smaller in size, they retained a substantial accumulation of smooth muscle cells and collagen, features consistent with a stable plaque phenotype. Finally, CX3CR1(+/-)/apoE(-/-) mice showed the same reduction in atherosclerosis as the CX3CR1(-/-)/apoE(-/-) mice. CONCLUSIONS: The CX3CR1-CX3CL1 pathway seems to play a direct and critical role in monocyte recruitment and atherosclerotic lesion development in a mouse model of human atherosclerosis. |
