International Journal of Medical Sciences

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13 December 2017

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Int J Med Sci 2016; 13(11):858-867. doi:10.7150/ijms.16724

Research Paper

Activation of the CXCL16/CXCR6 Pathway by Inflammation Contributes to Atherosclerosis in Patients with End-stage Renal Disease

Ze Bo Hu1*, Yan Chen1,2*, Yu Xiang Gong1, Min Gao1, Yang Zhang1, Gui Hua Wang1, Ri Ning Tang1, Hong Liu1, Bi Cheng Liu1, Kun Ling Ma1,✉

1. Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China;
2. Department of Nephrology, Taizhou First People's Hospital, Taizhou, 225300, China
*The first two authors contributed equally.

Abstract

Background: Chronic inflammation plays a critical role in the progression of atherosclerosis (AS). This study aimed to determine the effects of the 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 with concomitant microinflammation and to further investigate the potential effects of the purinergic receptor P2X ligand-gated ion channel 7 (P2X7R).

Methods: Forty-three ESRD patients were divided into the control group (n=17) and the inflamed group (n=26) based on plasma C-reactive protein (CRP) levels. Biochemical indexes and lipid profiles of the patients were determined. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used for preliminary evaluation of AS. Haematoxylin-eosin (HE) and Filipin staining were performed to assess foam cell formation. CXCL16/CXCR6 pathway-related protein expression, P2X7R protein expression and the expression of monocyte chemotactic protein-1 (MCP-1), tumour necrosis factor-α (TNF-α), and CD68 were detected by immunohistochemical and immunofluorescence staining.

Results: Inflammation increased both MCP-1 and TNF-α expression and macrophage infiltration in radial arteries. Additionally, foam cell formation significantly increased in the radial arteries of the inflamed group compared to that of the controls. Further analysis showed that protein expression of CXCL16, CXCR6, disintegrin and metalloproteinase-10 (ADAM10) in the radial arteries of the inflamed group was significantly increased. Furthermore, CXCL16 expression was positively correlated with P2X7R expression in the radial arteries of ESRD patients.

Conclusions: Inflammation contributed to foam cell formation in the radial arteries of ESRD patients via activation of the CXCL16/CXCR6 pathway, which may be regulated by P2X7R.

Keywords: ESRD, inflammation, CXC chemokine ligand 16, purinergic receptor P2X ligand-gated ion channel 7, atherosclerosis

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How to cite this article:
Hu ZB, Chen Y, Gong YX, Gao M, Zhang Y, Wang GH, Tang RN, Liu H, Liu BC, Ma KL. Activation of the CXCL16/CXCR6 Pathway by Inflammation Contributes to Atherosclerosis in Patients with End-stage Renal Disease. Int J Med Sci 2016; 13(11):858-867. doi:10.7150/ijms.16724. Available from http://www.medsci.org/v13p0858.htm