Decreased Atherosclerotic Lesion Formation in CX3CR1/Apolipoprotein E Double Knockout Mice
Open Access
- 25 February 2003
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 107 (7), 1009-1016
- https://doi.org/10.1161/01.cir.0000057548.68243.42
Abstract
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.This publication has 28 references indexed in Scilit:
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