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Involved stage | Component | Characteristics | Mechanisms in atherosclerosis | References |
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Recruitment | CCL2 | Small proteins with four completely conserved cysteine residues, expressed by a variety of cell types | Guide Ly6Chigh monocytes to migrate into the subendothelial space and promote the bone marrow release of Ly6Chigh monocytes to the blood circulation | [15–17, 25–27] |
CCL5 | Proteins secreted by monocyte, macrophages, T cells, and smooth muscle cells | Play a critical role in Ly6Clow monocytes’ adhesion and recruitment | [13, 30, 33, 34] |
CXC3L1 | Expressed by endothelial cells as a membrane-bound protein | Allow firm adhesion of monocytes on endothelial and smooth muscle cells independently of integrin activation and improve their survival from the bone marrow | [13, 14, 30–32] |
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Egress from the plaque | CCL19 | Produced by stromal cells within primary and secondary lymphoid organs | Promote chemotactic migration of the macrophage to egress from the plaque | [38–41] |
CCL21 | Produced by stromal cells within primary and secondary lymphoid organs and lymphatic endothelial cells (LECs) in peripheral tissues | Promote chemotactic migration of macrophage to egress from the plaque | [38–43] |
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Migration inhibition | Netrin-1 | Neuronal guidance molecules expressed in many cells such as endothelial cells and foam cells | Inhibit the migration of monocytes into the intima and egress of macrophage from the plaque | [5, 9, 14, 47, 49, 51, 52] |
Semaphorin-3A | Secreted proteins expressed by endothelial cells and immune cells like macrophages | Act as a barrier to prevent monocyte adhesion and migration into the arterial intima during the early stage of atherogenesis | [57–60] |
Semaphorin-3E | Secreted, highly conserved, and matrix-associated proteins by macrophages, especially M1 macrophages | Inhibit macrophages migration and egress of macrophage from the plaque | [61, 62] |
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