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

(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 un...

Full description

Bibliographic Details
Main Authors: Ke Hu, Yi Guo, Yuxuan Li, Shunchang Zhou, Chanjun Lu, Chuanqi Cai, Hongjun Yang, Yiqing Li, Weici Wang
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/13/1/5
_version_ 1797344737619869696
author Ke Hu
Yi Guo
Yuxuan Li
Shunchang Zhou
Chanjun Lu
Chuanqi Cai
Hongjun Yang
Yiqing Li
Weici Wang
author_facet Ke Hu
Yi Guo
Yuxuan Li
Shunchang Zhou
Chanjun Lu
Chuanqi Cai
Hongjun Yang
Yiqing Li
Weici Wang
author_sort Ke Hu
collection DOAJ
description (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.
first_indexed 2024-03-08T11:07:03Z
format Article
id doaj.art-3a8636ea6db9473ca173c1dcf4fbf71d
institution Directory Open Access Journal
issn 2076-3921
language English
last_indexed 2024-03-08T11:07:03Z
publishDate 2023-12-01
publisher MDPI AG
record_format Article
series Antioxidants
spelling doaj.art-3a8636ea6db9473ca173c1dcf4fbf71d2024-01-26T14:39:15ZengMDPI AGAntioxidants2076-39212023-12-01131510.3390/antiox13010005Identification and Validation of PTGS2 Gene as an Oxidative Stress-Related Biomarker for Arteriovenous Fistula FailureKe Hu0Yi Guo1Yuxuan Li2Shunchang Zhou3Chanjun Lu4Chuanqi Cai5Hongjun Yang6Yiqing Li7Weici Wang8Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, ChinaDepartment of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, ChinaDepartment of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, ChinaCenter of Experimental Animals, Huazhong University of Science and Technology, Wuhan 430000, ChinaDepartment of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, ChinaDepartment of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, ChinaKey Laboratory of Green Processing and Functional New Textile Materials of Ministry of Education, Wuhan Textile University, Wuhan 430200, ChinaDepartment of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, ChinaDepartment of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China(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.https://www.mdpi.com/2076-3921/13/1/5arteriovenous fistula failureoxidative stressprostaglandin-endoperoxide synthase 2
spellingShingle Ke Hu
Yi Guo
Yuxuan Li
Shunchang Zhou
Chanjun Lu
Chuanqi Cai
Hongjun Yang
Yiqing Li
Weici Wang
Identification and Validation of PTGS2 Gene as an Oxidative Stress-Related Biomarker for Arteriovenous Fistula Failure
Antioxidants
arteriovenous fistula failure
oxidative stress
prostaglandin-endoperoxide synthase 2
title Identification and Validation of PTGS2 Gene as an Oxidative Stress-Related Biomarker for Arteriovenous Fistula Failure
title_full Identification and Validation of PTGS2 Gene as an Oxidative Stress-Related Biomarker for Arteriovenous Fistula Failure
title_fullStr Identification and Validation of PTGS2 Gene as an Oxidative Stress-Related Biomarker for Arteriovenous Fistula Failure
title_full_unstemmed Identification and Validation of PTGS2 Gene as an Oxidative Stress-Related Biomarker for Arteriovenous Fistula Failure
title_short Identification and Validation of PTGS2 Gene as an Oxidative Stress-Related Biomarker for Arteriovenous Fistula Failure
title_sort identification and validation of ptgs2 gene as an oxidative stress related biomarker for arteriovenous fistula failure
topic arteriovenous fistula failure
oxidative stress
prostaglandin-endoperoxide synthase 2
url https://www.mdpi.com/2076-3921/13/1/5
work_keys_str_mv AT kehu identificationandvalidationofptgs2geneasanoxidativestressrelatedbiomarkerforarteriovenousfistulafailure
AT yiguo identificationandvalidationofptgs2geneasanoxidativestressrelatedbiomarkerforarteriovenousfistulafailure
AT yuxuanli identificationandvalidationofptgs2geneasanoxidativestressrelatedbiomarkerforarteriovenousfistulafailure
AT shunchangzhou identificationandvalidationofptgs2geneasanoxidativestressrelatedbiomarkerforarteriovenousfistulafailure
AT chanjunlu identificationandvalidationofptgs2geneasanoxidativestressrelatedbiomarkerforarteriovenousfistulafailure
AT chuanqicai identificationandvalidationofptgs2geneasanoxidativestressrelatedbiomarkerforarteriovenousfistulafailure
AT hongjunyang identificationandvalidationofptgs2geneasanoxidativestressrelatedbiomarkerforarteriovenousfistulafailure
AT yiqingli identificationandvalidationofptgs2geneasanoxidativestressrelatedbiomarkerforarteriovenousfistulafailure
AT weiciwang identificationandvalidationofptgs2geneasanoxidativestressrelatedbiomarkerforarteriovenousfistulafailure