Background: Vascular remodeling is an alteration in the structure of vessels in response to
injury or hemodynamic changes. Disturbance of the structural and functional integrity of the endothelial
cell layer can be observed in vascular remodeling associated with inflammation. Chemokines have
been implicated in a wide range of diseases with prominent inflammatory components, and also in vascular
remodeling. Among them, CC-chemokines are of great interest. They act through conventional
CC-chemokine receptors (CCRs), widely expressed by leucocytes which are attracted to sites of
chronic inflammation. However, many experimental data show that CCRs are expressed by vascular
cells, suggesting a direct, leukocyte-independent effect on vascular remodeling.
Objective: Here, we discuss the role of CC-chemokines in atherosclerosis, angiogenesis, restenosis and
renal dysfunction through direct activation of endothelial cells, endothelial progenitors, vascular
smooth muscle cells, platelets, erythrocytes, mesangial cells and fibroblasts.
Results: The pathophysiological role of CC-chemokines has become more interesting since the
discovery of the atypical chemokine receptor (ACKR) subfamily, that does not couple with G proteins
and fails to transmit conventional intracellular signals. It has been demonstrated to be a chemokine
scavenger or decoy receptor with a role in the regulation of acute inflammatory responses.
Conclusion: At the vascular level, ACKRs are expressed by endothelial cells and endothelial lymphatic
cells that seem to regulate angio- and lymph-angiogenesis. Pleiotropic effects of CC-chemokines on vascular
wall cells and leukocytes increase their importance in vascular remodeling and suggest new drugs to
counteract vascular dysfunction.