Contribution of CXCL16/CXCR6 pathway activated by inflammation to atherosclerosis in patients with end-stage renal disease

Abstract

Objective To investigate the effects of CXC chemokine ligand 16 (CXCL16)/CXC chemokine receptor 6 (CXCR6) pathway on cholesterol accumulation of atherosclerosis in the radial artery of end-stage renal disease (ESRD) patients under inflammatory stress and further investigate its potential mechanisms modulated by purinergic receptor P2X ligand-gated ion channel 7 (P2X7R). Methods According to plasma C-reactive protein (CRP), forty ESRD patients were divided into control group (CRP<3.0 mg/L, n=15) and inflammation group (CRP≥3.0 mg/L, n=25). Biochemical index and lipid spectrum of patients were measured. Tissues from the radial artery of patients receiving arteriovenostomy were removed surgically. Foam cell formation was observed by hematoxylin-eosin (HE) and cholesterol accumulation was assessed by filipin staining. CXCL16/CXCR6 pathway related protein expression, P2X7R protein expression and the expression of monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and CD68 were detected by immunohistochemistry staining and immunofluorescence staining. Results Compared with that in control group, protein expression of MCP-1 and TNF-α in radial arteries were increased in inflammation group accompanied with macrophage infiltration (P<0.05). Further more, there was significantly increased foam cell formation in continuous cross-sections of radial arteries in inflammation group, which was closely correlated with increased protein expression of CXCL16, CXCR6 and a disintegrin and metalloproteinase (ADAM)-10 (P<0.05). CXCL16 expression was positively correlated with CRP level (r=0.79, P<0.05) and P2X7R expression (r=0.65, P<0.05). Conclusion Inflammation contributes to foam cell formation in the radial artery of ESRD patients by activating the CXCL16/CXCR6 pathway, and promotes atherosclerosis, which is possibly regulated by P2X7R activation. Key words: Inflammation; Kidney failure, chronic; Atherosclerosis; Chemokine, CXC; Receptors, purinergic P2