Pharmacological Inhibition of the Chemokine Receptor, CX3CR1, Reduces Atherosclerosis in Mice

Objective—Alterations of the chemokine receptor CX3CR1 gene were associated with a reduced risk of myocardial infarction in human and limited atherosclerosis in mice. In this study, we addressed whether CX3CR1 antagonists are potential therapeutic tools to limit acute and chronic inflammatory processes in atherosclerosis. Approach and Results—Treatment with F1, an amino terminus–modified CX3CR1 ligand endowed with CX3CR1 antagonist activity, reduced the extent of atherosclerotic lesions in both Apoe−/− and Ldlr−/− proatherogenic mouse models. Macrophage accumulation in the aortic sinus was reduced in F1-treated Apoe−/− mice but the macrophage density of the lesions was similar in F1-treated and control mice. Both in vitro and in vivo F1 treatment reduced CX3CR1-dependent inflammatory monocyte adhesion, potentially limiting their recruitment. In addition, F1-treated Apoe−/− mice displayed reduced numbers of blood inflammatory monocytes, whereas resident monocyte numbers remained unchanged. Both in vitro an...