Ccr5 But Not Ccr1 Deficiency Reduces Development of Diet-Induced Atherosclerosis in Mice

Abstract

Objective— Chemokines and their receptors are crucially involved in the development of atherosclerotic lesions by directing monocyte and T cell recruitment. The CC-chemokine receptors 1 (CCR1) and 5 (CCR5) expressed on these cells bind chemokines implicated in atherosclerosis, namely CCL5/RANTES. Although general blockade of CCL5 receptors reduces atherosclerosis, specific roles of CCR1 and CCR5 have not been unequivocally determined. Methods and Results— We provide two independent lines of investigation to dissect the effects of Ccr1 and Ccr5 deletion in apolipoprotein E–deficient (ApoE−/−) mice in a collaboration between Aachen/Germany and Geneva/Switzerland. Different strains of ApoE−/−Ccr5−/− mice, ApoE−/−Ccr1−/− mice or respective littermates, were fed a high-fat diet for 10 to 12 weeks. Plaque areas were quantified in the aortic roots and thoracoabdominal aortas. Concordantly, both laboratories found that lesion formation was reduced in ApoE−/−Ccr5−/− mice. Plaque quality and immune cells were asses... Although general blockade of CCL5 receptors reduces atherosclerosis, specific roles of CCR1 and CCR5 have not been unequivocally determined. Genetic deletion of Ccr5 but not Ccr1 in ApoE−/− mice protects from diet-induced atherosclerosis, resulting in a more stable plaque phenotype with reduced mononuclear cell infiltration and Th1-type immune responses.