Table 1.

The roles of key chemokines in atherosclerosis.

Chemokine	Summary of studies using mouse model systems	Ref.
CCL2	Hematopoietic overexpression in ApoE−/− model accelerates atherosclerosis without affecting lipoprotein profile. Inhibition by transfection of an N-terminal deletion mutant in skeletal muscle of ApoE−/− mice limits progression and destabilization of established plaques and normalizes levels of pro-inflammatory mediators. Deficiency reduces atherosclerosis in ApoE−/− or LDLr−/− models. Local gene silencing using adenoviral vectors promotes plaque stabilization in the ApoE−/−.	[18], [19], [20], [21], [22], [23]
CCL3	BMT in the LDLr−/− model system shows that deficiency of CCL3 reduces atherosclerotic burden and decreases accumulation of neutrophils.	[24], [25]
CCL5	Knockdown of Y-box binding protein-1, which controls CCL5 expression, reduces neointima formation following carotid ligation in the ApoE−/− model.	[26]
CXCL5	Inhibition in the ApoE−/− model leads to macrophage foam cell accumulation in atherosclerotic plaques. The chemokine modulates macrophage activation and stimulates cholesterol efflux together with associated changes in gene expression.	[27]
CXCL1	Blocking antibodies increases neointimal formation and inhibits endothelial recovery after carotid injury in ApoE−/− model.	[28]
CXCL10	Deficiency in the ApoE−/− model reduces atherosclerosis by modulating the local balance of effector and regulatory T cells with increased levels of TGF-β and IL-10. Inhibition using neutralizing antibodies in the ApoE−/− produces a stable plaque phenotype.	[29], [30]
CXCL16	Deficiency in the LDLr−/− model exacerbates lesion formation. Overexpression promotes a vulnerable plaque phenotype in the ApoE−/− model.	[31], [32]
CX3CL1	Deficiency in the ApoE−/− or LDLr−/− models reduces atherosclerosis in the brachiocephalic artery but not in the aortic root.	[33]
CCL17	Deficiency in the ApoE−/− model reduces atherosclerosis that is dependent on Tregs. Expression of CCL17 by DCs limits expansion of Tregs and enhances atherosclerosis. CCL17 blocking antibody expands Tregs and reduces atherosclerosis.	[34]
CCL19/CCL21	Transplantation of bone marrow from mice lacking both these chemokines in the LDLr−/− model increases inflammatory cellular infiltration but decreases expression of several pro-inflammatory cytokines. Plaque stability is increased but lesion development remains unchanged.	[35]
CXCL12	Administration in the ApoE−/− model promotes a more stable plaque phenotype and enhances the accumulation of smooth muscle progenitor cells without promoting atherosclerosis.	[36]
CXCL4	Elimination from platelets reduces atherosclerosis in C57BL/6 and ApoE−/− mice.	[37]
MIF	Deficiency in the LDLr−/− model reduces atherosclerosis associated with impaired monocyte adhesion to the arterial wall. Blockade in mice with advanced atherosclerosis leads to plaque regression and reduces monocyte and T-cell content in plaques. Blockade in the LDLr−/− model following experimental angioplasty decreases vascular inflammation, cellular proliferation and neointimal thickening. Inhibition in the ApoE−/− model reduces aortic inflammation and, following vascular injury, shifts the cellular composition of neointimal plaques to a stable phenotype with reduced inflammatory cells and increased SMC content.	[38], [39], [40], [41], [42]