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.

Galectin-3 in Peripheral Artery Disease. Relationships with Markers of Oxidative Stress and Inflammation

“…Reports indicate that human carotid plaques express galectin-3 in smooth muscle cells, especially in macrocalcified areas, where it co-localizes with alkaline phosphatase [16]. Of note from an early study from our group is the observation of calcium deposition in the media of arteries from PAD patients; a distinct and frequent finding in affected arteries [32]. In the same study, we reported an increase in CD68-positive cells in diseased arteries; the conclusion drawn is that, under certain stimuli, arterial smooth muscle cells can shift their phenotypes to a macrophage-cell state [33].…”

“…Control tissue samples were processed identically to the test samples, except that the primary antibodies were omitted from the incubation. The immunohistochemical expressions of CD68 antigen and α-actin were used as markers of macrophages and smooth muscle cells, respectively, and analyzed as previously reported [32,44]. …”

Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study

“…In agreement with this hypothesis, several articles have shown a decrease in the levels of CCL2 and CXCL8 (IL-8) in serum from persons with the rs12075 G allele [26,39,40,41]. Besides, the rs12075 G allele has also been related with low CCL2 levels in patients with chronic inflammatory diseases such as ischemia of the lower extremities [42] and obesity [43], as well as low leukocyte counts in African people [44].…”

Exploring the Process of Energy Generation in Pathophysiology by Targeted Metabolomics: Performance of a Simple and Quantitative Method

“…Participants with diabetes mellitus were excluded to avoid metabolic bias and to limit variability. Further clinical details on the inclusion and exclusion criteria have been previously described [20].…”