Identification and Validation of PTGS2 Gene as an Oxidative Stress-Related Biomarker for Arteriovenous Fistula Failure

Abstract

(1) Background: Arteriovenous fistulas (AVFs) are the preferred site for hemodialysis. Unfortunately, approximately 60% of patients suffer from AVF failure within one year. Oxidative stress plays an important role in the occurrence and development of AVF. However, the underlying mechanisms remain unclear. Therefore, specific oxidative stress-related biomarkers are urgently needed for the diagnosis and treatment of AVF failure. (2) Methods: Bioinformatics analysis was carried out on dataset GSE119296 to screen for PTGS2 as a candidate gene related to oxidative stress and to verify the expression level and diagnostic efficacy of PTGS2 in clinical patients. The effects of NS398, a PTGS2 inhibitor, on hemodynamics, smooth muscle cell proliferation, migration, and oxidative stress were evaluated in a mouse AVF model. (3) Results: Based on 83 oxidative stress-related differentially expressed genes, we identified the important pathways related to oxidative stress. PTGS2 may have diagnostic and therapeutic efficacy for AVF failure. We further confirmed this finding using clinical specimens and validation datasets. The animal experiments illustrated that NS398 administration could reduce neointimal area (average decrease: 49%) and improve peak velocity (average increase: 53%). (4) Conclusions: Our study identified PTGS2 as an important oxidative stress-related biomarker for AVF failure. Targeting PTGS2 reduced oxidative stress and improved hemodynamics in an AVF mouse model.

Keywords

• arteriovenous fistula failure
• oxidative stress
• prostaglandin-endoperoxide synthase 2