Abstract: TH-PO326
p-Cresyl Sulfate Induced Oxidative Stress and Inflammation on Endothelial and Vascular Smooth Muscle Cells
Session Information
- Vascular Access - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 704 Dialysis: Vascular Access
Authors
- Lee, Shina, Ewha Womans University Mokdong Hospital, Seoul, Korea (the Republic of)
- Kim, Seung-Jung, Ewha Womans University Mokdong Hospital, Seoul, Korea (the Republic of)
Background
Vascular access dysfunction affects negatively patient morbidity and mortality. The most common problem in AVF and AVG is venous stenosis, resulting from a neointimal hyperplasia development. Recent study reported that p-Cresyl sulfate was related to the outcome of vascular access in hemodialysis patients.
p-cresyl sulfate (p-CS), poorly removed by conventional dialysis, has been known to exhibit pro-oxidant properties in renal tubular cells by enhancing NAD(P)H oxidase activity and induce reactive oxygen species(ROS) production in endothelial cells. However, the mechanism of vascular toxicity induced by p-CS was poorly understood.
The aim of the study was to determine whether p-CS enhances the production of ROS in vascular endothelial cell and proliferation of smooth muscle cell resulting in neointimal hyperplasia. Additionally, we aimed to determine whether p-CS induces the expression of ICAM-1 and MCP-1 by ROS induced activation of NK-KB in endothelial cell.
Methods
Aortic smooth muscle cells (SMCs) were treated with p-CS (10-1000 μmol/L), and aortic SMC proliferation was measured Bromodeoxyuridine cell proliferation assay. Western blot analysis was done for ERK1/2 and p38 MAPK.
Human umbilical vein endothelial cells (HUVEC) were also treated with p-CS (1000 μmol/L). The productions of NF-κB, ICAM-1, MCP-1 and eNOS in HUVEC were assessed using RT-PCR and ELISA.
Results
p-CS stimulated the proliferation of aortic SMCs in a dose dependent manner, and promoted the phosphorylation of ERK1/2 and p38 MAPK. In HUVEC, p-Cresyl sulfate induces ROS production by enhancing NAD(P)H oxidase and upregulates the expression of ICAM-1 and MCP-1 by ROS-induced activation of NF-kB. However, NO synthase seemed not to be involved in p-cresyl sulfate induced oxidative stress in HUVEC.
Conclusion
Our data confirmed that p-CS was attributed to vascular SMC proliferation and inflammation and oxidative stress in HUVECs in vitro. Further evaluation will be needed to clarify the role of p-CS in vascular access stenosis and neointimal hyperplasia.