Increased expression of the P2Y₁₂ receptor is involved in the failure of autogenous arteriovenous fistula caused by stenosis

作者全名："Liu, Lei; Gao, Jianya; Tang, Yuewu; Guo, Guangfeng; Gan, Hua"

作者地址："[Liu, Lei; Gao, Jianya; Guo, Guangfeng; Gan, Hua] Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 1, Chongqing, Peoples R China; [Liu, Lei; Gao, Jianya; Tang, Yuewu] Chongqing Univ, Dept Nephrol, Three Gorges Hosp, Chongqing, Peoples R China; [Liu, Lei; Gao, Jianya; Tang, Yuewu] Chongqing Three Gorges Cent Hosp, Dept Nephrol, Chongqing, Peoples R China; [Gan, Hua] Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Gan, H (通讯作者)，Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 1, Chongqing, Peoples R China.; Gan, H (通讯作者)，Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：RENAL FAILURE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001123478400001

JCR分区：Q1

影响因子：3

年份：2023

卷号：45

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：P2Y(12); stenosis; arteriovenous fistula (AVF); neointima; hemodialysis

摘要："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-beta 1 (TGF-beta 1), monocyte chemotactic protein 1 (MCP-1), and CD68 in the venous tissues. The expression levels of P2Y(12), TGF beta 1, 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), TGF beta 1, 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-beta 1(+) 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."

基金机构：Chongqing Science and Technology Bureau Project [cstc2020jscx-kjfpX0021]

基金资助正文：This work was supported by the Chongqing Science and Technology Bureau Project under Grant [number cstc2020jscx-kjfpX0021].