Several members of the chemokine family are involved in regulation of fibrosis. This review manuscript discusses the role of the chemokines in the pathogenesis of myocardial fibrosis. The CC chemokine CCL2 exerts fibrogenic actions through recruitment and activation of monocytes and macrophages expressing its receptor, CCR2. Other CC chemokines may also contribute to fibrotic remodeling by recruiting subsets of fibrogenic macrophages. CXC chemokines containing the ELR motif may exert pro-fibrotic actions, through recruitment of activated neutrophils and subsequent formation of neutrophil extracellular traps (NETs), or via activation of fibrogenic monocytes. CXCL12 has also been suggested to exert fibrogenic actions through effects on fibroblasts and immune cells. In contrast, the CXCR3 ligand CXCL10 was found to reduce cardiac fibrosis, inhibiting fibroblast migration. Chemokines are critical links between inflammation and fibrosis in myocardial disease and may be promising therapeutic targets for patients with heart failure accompanied by prominent inflammation and fibrosis.
Keywords: chemokine; extracellular matrix; fibroblast; fibrosis; heart failure; macrophage; myocardial infarction.