title: Activation of the CXCL16/CXCR6 Pathway by Inflammation Contributes to Atherosclerosis in Patients with End-stage Renal Disease.
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.
authors.affiliation: Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Ze Bo
authors.initials: ZB
authors.lastname: Hu
authors.affiliation: Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China;; Department of Nephrology, Taizhou First People's Hospital, Taizhou, 225300, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Yu Xiang
authors.initials: YX
authors.lastname: Gong
authors.affiliation: Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Gui Hua
authors.initials: GH
authors.lastname: Wang
authors.affiliation: Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Ri Ning
authors.initials: RN
authors.lastname: Tang
authors.affiliation: Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Bi Cheng
authors.initials: BC
authors.lastname: Liu
authors.affiliation: Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Kun Ling
authors.initials: KL
authors.lastname: Ma
mesh_terms: D000072197:ADAM10 Protein / Q000378:metabolism; D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D018932:Chemokine CCL2; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008565:Membrane Proteins; C546468:P2RX7 protein, human; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D058486:Receptors, Purinergic P2X7; D051116:Receptors, Scavenger; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
keywords: CXC chemokine ligand 16; ESRD; atherosclerosis; inflammation; purinergic receptor P2X ligand-gated ion channel 7