The Role Of Activation Of CXCL16/CXCR6 Pathway In The Progression Of Atherosclerosis In Patients With End-stage Renal Disease Under Micro-inflammation

Objective Inflammation plays a critical role in the progression of atherosclerosis(AS).This study aimed to observe the effects of CXC chemokine ligand 16(CXCL16)/CXC chemokine receptor 6(CXCR6)pathway on cholesterol accumulation in the radial arteries of end-stage renal disease(ESRD)patients under micro-inflammation and further investigate its potential mechanisms modulated by purinergic receptor P2X ligand-gated ion channel 7(P2X7R).Methods 43 ESRD patients were divided into control group(n=17)and inflamed group(n=26)according to plasma C-reactive protein(CRP)level.Biochemical index and lipid profile of patients were measured.Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in the experiments for preliminary evaluation of AS.Foam cell formation was observed by Hematoxylin-eosin(HE)and Filipin staining.CXCL16/CXCR6 pathway related protein expressions,P2X7R protein expressions and the expressions of monocyte chmotactic protein 1(MCP-1),tumor necrosis factor-α(TNF-α),and CD68 were detected by immunohistochemical staining and immunofluorescent staining.Results Immunohistochemical staining demonstrated that inflammation increased both protein expressions of MCP-1 and TNF-a in radial arteries of inflamed group accompanied with macrophage infiltration.Further analysis showed that there were significantly increased foam cell formation in continuous cross-sections of radial arteries of inflamed group compared to the controls,which were closely correlated with increased protein expressions of CXCL16,CXCR6,and disintegrin and metalloproteinase-10(ADAM 10).We also found that CXCL16 expression was positively correlated with P2X7R expression in the radial arteries of ESRD patients.Conclusions Microinflammation contributed to foam cell formation in the radial arteries of ESRD patients via the activation of the CXCL16/CXCR6 pathway,which is possibly regulated by P2X7R activation.