The development of atherosclerotic plaques involves blood monocytes expressing the surface protein CX3CR1 binding to blood vessel endothelial cells-expressing mCX3CL1. Riopel et al. investigated the effects of administration of a long acting CX3CL1, tethered to the mouse Fc fragment (CX3CL1-Fc). They find that CX3CL1-Fc decreases monocyte adhesion to the endothelium both in vitro and in vivo. Moreover, they also demonstrate that CX3CL1-Fc treatment reduced atherosclerosis in hypercholesterolemic Ldlr KO mice without changes in plasma cholesterol levels.