Regulation of the migration and survival of monocyte subsets by chemokine receptors and its relevance to atherosclerosis.
Monocytes are central mediators in the advance of atherosclerotic plaque, making them a natural therapeutic target for reducing disease burden. Here, we highlight recent advances in our current understanding of monocyte heterogeneity and its relevance to regulation of monocyte accumulation and function within atherosclerotic plaques. Differences that distinguish monocyte subsets include differential expression of chemokine receptors, especially CCR2 and CX3CR1. Ablation of expression of these 2 receptors (or their ligands) in mice has an additive inhibition on monocyte recruitment to atherosclerotic plaques. Moreover, simultaneously interfering with 3 key pathways--CCR2, CX3CR1, and CCR5--essentially abolishes atherosclerosis in mice. Here, we discuss how these chemokine receptors act at multiple points on at least 1 monocyte subset, regulating their mobilization from bone marrow, survival, or recruitment to plaques. Finally, we discuss how this knowledge may be useful clinically, emphasizing that CX3CR1 may in particular be a viable target for therapeutic manipulation of monocyte-derived cell fate in cardiovascular disease.
Gautier
Emmanuel L
EL
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
Jakubzick
Claudia
C
Randolph
Gwendalyn J
GJ
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology*; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement; D002470:Cell Survival; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000145:classification / Q000502:physiology*; D054390:Receptors, CCR2 / Q000502:physiology; D019707:Receptors, Chemokine / Q000502:physiology*; D051131:Receptors, Oxidized LDL / Q000378:metabolism; D051116:Receptors, Scavenger / Q000502:physiology
D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D051131:Receptors, Oxidized LDL; D051116:Receptors, Scavenger