Decreased atherosclerotic lesion formation in CX3CR1/apolipoprotein E double knockout mice

Article

关键词: MONOCYTE CHEMOATTRACTANT PROTEIN-1;    FRACTALKINE RECEPTOR CX(3)CR1;    CORONARY-ARTERY DISEASE;    LOW-DENSITY-LIPOPROTEIN;    CHEMOKINE FRACTALKINE;    TARGETED DELETION;    DEFICIENT MICE;    POLYMORPHISM;    HYPERCHOLESTEROLEMIA;    ACCUMULATION;   

DOI  :  10.1161/01.CIR.0000057548.68243.42

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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