Understanding the role of circulating chemokine (C-C motif) ligand 2 in patients with chronic ischemia threatening the lower extremities

• Published in: Vascular medicine (London, England) Vol. 19; no. 6; pp. 442 - 451
• Main Authors: Rull, Anna, Hernandez-Aguilera, Anna, Fibla, Montserrat, Sepulveda, Julio, Rodríguez-Gallego, Esther, Riera-Borrull, Marta, Sirvent, Juan J, Martín-Paredero, Vicente, Menendez, Javier A, Camps, Jordi, Joven, Jorge
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.12.2014; Sage Publications Ltd
• Subjects: Aged; Aged, 80 and over; Biomarkers - blood; Chemokine CCL2 - blood; Chemokine CCL2 - genetics; Chronic Disease; Female; Genetic Variation - genetics; Genotype; Humans; Ischemia - blood; Ischemia - genetics; Lower Extremity - blood supply; Male; Middle Aged; Monocytes - metabolism; Peripheral Arterial Disease - blood; Peripheral Arterial Disease - genetics; Polymorphism, Single Nucleotide - genetics; Risk Factors; atherosclerosis; risk factors; genetics; peripheral artery disease; biological markers; cytokines; metabolism
• ISSN: 1358-863X; 1477-0377; 1477-0377
• DOI: 10.1177/1358863X14554034

The role of chemokine (C-C motif) ligand 2 (CCL2) in peripheral artery disease is unclear. We measured the difference between serum and plasma levels of CCL2 in patients with chronic ischemia threatening the lower extremities following the observation that atypical chemokine receptors in blood and tissue cells may prevent CCL2 from entering the circulation and consequently modulate its function of attracting monocytes to the site of lesion. To identify the influence of CCL2, we compared the patients’ values to those in bio-banked samples from a control population. Further, we explored the association with the Asp42Gly polymorphism (rs12075) in Duffy antigen chemokine receptor; one of these atypical chemokine receptors. When possible, we evaluated in surgically excised normal and affected arteries the calcium burden as well as the expression of CCL2 and related receptors reflecting the inflammatory status. Our findings indicate that circulating CCL2 was significantly associated with the severity and presence of the disease (OR 0.966, 95% CI 0.944 to 0.988, p = 0.003). Circulating CCL2 was dependent on the rs12075 genotype (AA>AG>GG), which, probably, indicates a higher expression of chemokine receptor in the arteries of AA subjects. The associations with genetic variants and the over-expression of atypical chemokine receptors in diseased arteries may have potential implications and our data indicate that CCL2 may represent a previously unrecognized factor that needs to be considered in the screening of patients with risk factors for peripheral artery disease.