Influence of sodium ferulate on neutrophil extracellular traps-platelet activation-mediated endothelial dysfunction in immune small vasculitis.

IF 2.5 4区医学 Q2 PATHOLOGY

Cytojournal Pub Date : 2024-12-27 eCollection Date: 2024-01-01 DOI:10.25259/Cytojournal_153_2024

Xiaoli Zhou, Zhuojun Wang, Weixiang Liao, Qianlu Yin, Chuan Xiong, Yuhang Zheng, Wei Peng

{"title":"Influence of sodium ferulate on neutrophil extracellular traps-platelet activation-mediated endothelial dysfunction in immune small vasculitis.","authors":"Xiaoli Zhou, Zhuojun Wang, Weixiang Liao, Qianlu Yin, Chuan Xiong, Yuhang Zheng, Wei Peng","doi":"10.25259/Cytojournal_153_2024","DOIUrl":null,"url":null,"abstract":"Objective: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease that is challenging to treat. This study aimed to identify the effect of sodium ferulate on endothelial dysfunction mediated by neutrophil extracellular trap (NET)-platelet activation in AAV to provide potential strategies for AAV treatment.Material and methods: An animal model of myeloperoxidase (MPO)-AAV passive immune vasculitis was established using anti-MPO immunoglobulin G and Rag2 knockout mice. The efficacy and mechanism of action of sodium ferulate in AAV were explored in cultured and isolated endothelial progenitor cells (EPCs), and messenger ribonucleic acid gene expression, relative protein expression, and protein fluorescence intensity were determined through quantitative polymerase chain reaction, Western blotting, and immunofluorescence, respectively. Serum antibody concentrations were determined by enzyme-linked immunosorbent assay, and flow cytometry was used in determining the expression levels of platelet-selectin (CD62p) and procaspase-activating compound-1 (PAC-1) on the surfaces of the platelets. The EPCs' ultramicroscopic structure was observed through transmission electron microscopy.Results: The expression levels of ANCA, histone H3 citrullinated, and MPO protein fluorescence intensity in MPO-AAV mice were inhibited by sodium ferulate, and the expression levels of CD62p and PAC-1 on the cell surface were reduced. The relative expression levels of β-trace protein (β-TG), soluble thrombomodulin, inducible nitric oxide synthase (iNOS), and tumor necrosis factor α decreased. We found that sodium ferulate inhibited NETs' free DNA and mitigated damage in EPCs. In addition, relative expression levels of von Willebrand Factor, β-TG, and iNOS and serum concentrations of PAC-1, β-TG, and iNOS were inhibited.Conclusion: Sodium ferulate can treat AAV by inhibiting NET release and platelet activation and reducing endothelial cell damage.","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"76"},"PeriodicalIF":2.5000,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801691/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytojournal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.25259/Cytojournal_153_2024","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease that is challenging to treat. This study aimed to identify the effect of sodium ferulate on endothelial dysfunction mediated by neutrophil extracellular trap (NET)-platelet activation in AAV to provide potential strategies for AAV treatment.

Material and methods: An animal model of myeloperoxidase (MPO)-AAV passive immune vasculitis was established using anti-MPO immunoglobulin G and Rag2 knockout mice. The efficacy and mechanism of action of sodium ferulate in AAV were explored in cultured and isolated endothelial progenitor cells (EPCs), and messenger ribonucleic acid gene expression, relative protein expression, and protein fluorescence intensity were determined through quantitative polymerase chain reaction, Western blotting, and immunofluorescence, respectively. Serum antibody concentrations were determined by enzyme-linked immunosorbent assay, and flow cytometry was used in determining the expression levels of platelet-selectin (CD62p) and procaspase-activating compound-1 (PAC-1) on the surfaces of the platelets. The EPCs' ultramicroscopic structure was observed through transmission electron microscopy.

Results: The expression levels of ANCA, histone H3 citrullinated, and MPO protein fluorescence intensity in MPO-AAV mice were inhibited by sodium ferulate, and the expression levels of CD62p and PAC-1 on the cell surface were reduced. The relative expression levels of β-trace protein (β-TG), soluble thrombomodulin, inducible nitric oxide synthase (iNOS), and tumor necrosis factor α decreased. We found that sodium ferulate inhibited NETs' free DNA and mitigated damage in EPCs. In addition, relative expression levels of von Willebrand Factor, β-TG, and iNOS and serum concentrations of PAC-1, β-TG, and iNOS were inhibited.

Conclusion: Sodium ferulate can treat AAV by inhibiting NET release and platelet activation and reducing endothelial cell damage.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Cytojournal PATHOLOGY-

CiteScore

2.20

自引率

42.10%

发文量

审稿时长

>12 weeks

期刊介绍： The CytoJournal is an open-access peer-reviewed journal committed to publishing high-quality articles in the field of Diagnostic Cytopathology including Molecular aspects. The journal is owned by the Cytopathology Foundation and published by the Scientific Scholar.

文献相关原料

公司名称

产品信息

索莱宝

MTT solution

索莱宝

PicoGreen double-stranded DNA quantitative detection kit

索莱宝

DiI-ACLDL