PMID- 38532720 OWN - NLM STAT- MEDLINE DCOM- 20240328 LR - 20240508 IS - 1525-6049 (Electronic) IS - 0886-022X (Print) IS - 0886-022X (Linking) VI - 45 IP - 2 DP - 2023 TI - Increased expression of the P2Y(12) receptor is involved in the failure of autogenous arteriovenous fistula caused by stenosis. PG - 2278314 LID - 10.1080/0886022X.2023.2278314 [doi] LID - 2278314 AB - OBJECTIVE: This study investigated the role of the P2Y(12) receptor in autogenous arteriovenous fistula (AVF) failure resulting from stenosis. METHODS: Stenotic venous tissues and blood samples were obtained from patients with end-stage renal disease (ESRD) together with AVF stenosis, while venous tissues and blood samples were collected from patients with ESRD undergoing initial AVF surgery as controls. Immunohistochemistry and/or immunofluorescence techniques were utilized to assess the expression of P2Y(12), transforming growth factor-beta1 (TGF-beta1), monocyte chemotactic protein 1 (MCP-1), and CD68 in the venous tissues. The expression levels of P2Y(12), TGFbeta1, and MCP-1 were quantified using quantitative reverse transcription-polymerase chain reaction and western blot analyses. Double and triple immunofluorescence staining was performed to precisely localize the cellular localization of P2Y(12) expression. RESULTS: Expression levels of P2Y(12), TGFbeta1, MCP-1, and CD68 were significantly higher in stenotic AVF venous tissues than in the control group tissues. Double and triple immunofluorescence staining of stenotic AVF venous tissues indicated that P2Y(12) was predominantly expressed in alpha-SMA-positive vascular smooth muscle cells (VSMCs) and, to a lesser extent, in CD68-positive macrophages, with limited expression in CD31-positive endothelial cells. Moreover, a subset of macrophage-like VSMCs expressing P2Y(12) were observed in both stenotic AVF venous tissues and control venous tissues. Additionally, a higher number of P2Y(12)(+)/TGF-beta1(+) double-positive cells were identified in stenotic AVF venous tissues than in the control group tissues. CONCLUSION: Increased expression of P2Y(12) in stenotic AVF venous tissues of patients with ESRD suggests its potential involvement in the pathogenesis of venous stenosis within AVFs. FAU - Liu, Lei AU - Liu L AD - Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - Department of Nephrology, Chongqing University Three Gorges Hospital, Chongqing, China. AD - Department of Nephrology, Chongqing Three Gorges Central Hospital, Chongqing, China. FAU - Gao, Jianya AU - Gao J AD - Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. AD - Department of Nephrology, Chongqing University Three Gorges Hospital, Chongqing, China. AD - Department of Nephrology, Chongqing Three Gorges Central Hospital, Chongqing, China. FAU - Tang, Yuewu AU - Tang Y AD - Department of Nephrology, Chongqing University Three Gorges Hospital, Chongqing, China. AD - Department of Nephrology, Chongqing Three Gorges Central Hospital, Chongqing, China. FAU - Guo, Guangfeng AU - Guo G AD - Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Gan, Hua AU - Gan H AD - Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. LA - eng PT - Journal Article DEP - 20231123 PL - England TA - Ren Fail JT - Renal failure JID - 8701128 RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Humans MH - Renal Dialysis MH - Constriction, Pathologic MH - Endothelial Cells MH - Transforming Growth Factor beta1 MH - *Arteriovenous Shunt, Surgical MH - *Kidney Failure, Chronic MH - *Arteriovenous Fistula PMC - PMC11073481 OTO - NOTNLM OT - P2Y12 OT - arteriovenous fistula (AVF) OT - hemodialysis OT - neointima OT - stenosis COIS- No potential conflict of interest was reported by the author(s). EDAT- 2023/01/01 00:00 MHDA- 2024/03/28 06:44 PMCR- 2023/11/23 CRDT- 2024/03/27 03:43 PHST- 2024/03/28 06:44 [medline] PHST- 2023/01/01 00:00 [pubmed] PHST- 2024/03/27 03:43 [entrez] PHST- 2023/11/23 00:00 [pmc-release] AID - 2278314 [pii] AID - 10.1080/0886022X.2023.2278314 [doi] PST - ppublish SO - Ren Fail. 2023;45(2):2278314. doi: 10.1080/0886022X.2023.2278314. Epub 2023 Nov 23.