Figure 1.

Chemokine receptor 5, a double-edged sword in the inflammatory response and endothelial repair during the process of metabolic syndrome and cardiovascular disease. (A) The proinflammatory role of CCR5 and its ligands in metabolic syndrome and cardiovascular disease. As shown in section (A), obesity is characterized as low-grade systemic or chronic inflammation that is associated with increased incidence of metabolic syndrome and cardiovascular disease. CCR5 and its ligands are associated with systemic inflammation. (1) CCR5 and its ligands promote the transition of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype and aggravate obesity-induced insulin resistance; (2) CCR5 and its ligands promote infiltration of leukocytes into plaques and endothelial permeability, decrease the content of smooth muscle cells and collagen content, indicating a more vulnerable plaque phenotype; (3) CCL5 increases the synthesis of triglyceride and hepatic steatosis through binding to its receptor, CCR5; (4) CCL5 could induce smooth muscle cell proliferation and promote the phenotypic switching from the contractile to the synthetic phenotype; (B) CCR5 and its ligands are involved in the endothelial repair during the process of endothelial damage. As shown in section (B), CCL3, CCL4, and CCL5 contain NF-κB binding motifs and are upregulated when induced by an inflammatory stimulus. Increased expression of CCL3/CCL4/CCL5 mediates the mobilization and recruitment of bone marrow derived-endothelial progenitor cells into the damaged endothelium by binding with its receptor, CCR5. In addition, CCL3, CCL4, and CCL5 could directly stimulate injured cells, increase nitric oxide production, and promote endothelial cell migration and proliferation to the injured sites.