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

Abstract

Objective This study investigated the role of the P2Y12 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 P2Y12, transforming growth factor-β1 (TGF-β1), monocyte chemotactic protein 1 (MCP-1), and CD68 in the venous tissues. The expression levels of P2Y12, TGFβ1, 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 P2Y12 expression.Results Expression levels of P2Y12, TGFβ1, 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 P2Y12 was predominantly expressed in α-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 P2Y12 were observed in both stenotic AVF venous tissues and control venous tissues. Additionally, a higher number of P2Y12+/TGF-β1+ double-positive cells were identified in stenotic AVF venous tissues than in the control group tissues.Conclusion Increased expression of P2Y12 in stenotic AVF venous tissues of patients with ESRD suggests its potential involvement in the pathogenesis of venous stenosis within AVFs.

Keywords

• P2Y12
• stenosis
• arteriovenous fistula (AVF)
• neointima
• hemodialysis