title: Understanding the role of circulating chemokine (C-C motif) ligand 2 in patients with chronic ischemia threatening the lower extremities.
abstract: 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.
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Rull
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain Servei d'Angiologia, Cirurgia Vascular i Endovascular, Hospital Universitari Joan XXIII, Tarragona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Hernandez-Aguilera
authors.affiliation: Servei d'Anatomia Patològica, Hospital Universitari Joan XXIII, Tarragona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fibla
authors.affiliation: Servei d'Angiologia, Cirurgia Vascular i Endovascular, Hospital Universitari Joan XXIII, Tarragona, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Sepulveda
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Rodríguez-Gallego
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Riera-Borrull
authors.affiliation: Servei d'Anatomia Patològica, Hospital Universitari Joan XXIII, Tarragona, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Sirvent
authors.affiliation: Servei d'Angiologia, Cirurgia Vascular i Endovascular, Hospital Universitari Joan XXIII, Tarragona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Martín-Paredero
authors.affiliation: Molecular Oncology Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menendez
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Camps
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari de Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain jorge.joven@urv.cat jcamps@grupsagessa.cat.
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood* / Q000235:genetics; D002908:Chronic Disease; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007511:Ischemia / Q000097:blood* / Q000235:genetics; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2
keywords: atherosclerosis; biological markers; cytokines; genetics; metabolism; peripheral artery disease; risk factors