Atheroprotective Roles of Adiponectin via CCL2 Inhibition

Abstract

Aim: Adiponectin (APN) exhibits different atheroprotective effects, and we have previously reported that APN function is modulated by its binding proteins, E-selectin ligand 1, Mac-2 binding protein, and cystatin C. In the present study, we aimed to identify a novel atheroprotective mechanism of APN via C–C motif chemokine 2 (CCL2). Methods: We conducted iMAP ® -intravascular ultrasound (IVUS) in 111 Japanese male patients with stable angina. The plaque characteristics were determined where “plaque burden” [(EEM CSA − lumen CSA)/(EEM CSA)×100 (%)] ＞50%, and their correlation with serum CCL2 and APN levels was analyzed. Using western blot analysis, the effects of APN on the biological effects of CCL2 were examined in their mutual binding by co-immunoprecipitation assay, the monocyte migration, and the phosphorylation of MAP kinases. Results: In a clinical study, we found that the percentage of plaque in the culprit lesion was correlated positively with serum CCL2 and negatively with serum APN levels, with significance. We identified CCL2 as a novel APN-binding serum protein using immunoprecipitation and western blot analysis. CCL2-induced phosphorylation of MAP kinases and monocyte migration was significantly attenuated by APN in vitro . Conclusion: The opposite association of APN and CCL2 on the percentage of coronary plaque might be caused by their direct interaction and competitive functions on monocyte migration.

Usefulness of MCP-1 Chemokine in the Monitoring of Patients with Coronary Artery Disease Subjected to Intensive Dietary Intervention: A Pilot Study

“…De Lemos et al have shown that an increased level of MCP-1 in subjects with acute coronary syndrome, in the fourth quartile (>238 pg/mL, which corresponds to the 90th percentile in the normal healthy population), is correlated with a significantly higher risk of death [ 30 ]. The baseline level of MCP-1 in our study was 159.6 pg/mL and was lower than in the Fujita study [ 31 ] of patients with stable CAD (240.8 pg/mL) and in the study by Fuchs et al [ 32 ] conducted among patients with manifested CAD and coronary artery stenosis >50% in angiography (609.7 pg/mL). Lower values were shown in the study of Tajfard et.…”