Fxyd5 downregulation protects the heart from ischemia/reperfusion injury by suppressing myocardial inflammation

IF 1.4 4区医学 Q4 IMMUNOLOGY

Transplant immunology Pub Date : 2025-09-03 DOI:10.1016/j.trim.2025.102282

Lei Zhang , Junjie Xu , Fujiang Cui , Jin Jin , Liwen Liu , Lei Wang , Yuxia Gao

{"title":"Fxyd5 downregulation protects the heart from ischemia/reperfusion injury by suppressing myocardial inflammation","authors":"Lei Zhang , Junjie Xu , Fujiang Cui , Jin Jin , Liwen Liu , Lei Wang , Yuxia Gao","doi":"10.1016/j.trim.2025.102282","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Myocardial ischemia/reperfusion (I/R) injury is a common cause of death. FXYD domain-containing ion transport regulator-5 (Fxyd5) is a type I membrane protein that plays a significant role in mediating cellular functions. However, the expression and function of Fxyd5 in myocardial I/R injury remain unclear.</div></div><div><h3>Methods</h3><div>Male C57BL/6 mice (8–10 weeks) were subjected to myocardial I/R by ligating the left anterior descending coronary artery. Preventive intervention was performed using adeno-associated virus 9 (AAV9)-mediated Fxyd5 knockdown. An in vitro hypoxia/reoxygenation (H/R) in H9c2 cardiomyoblasts was used for validation.</div></div><div><h3>Results</h3><div>Myocardial I/R injury significantly upregulated Fxyd5 expression (<em>p</em> < 0.01). Silencing Fxyd5 markedly improved cardiac function, as evidenced by a 58.0 % increase in EF (<em>p</em> < 0.01) and a 54.5 % reduction in infarct size (<em>p</em> < 0.01). Fxyd5 knockdown also attenuated myocardial apoptosis and inflammation, demonstrated by decreased cleaved caspase-3 expression and reduced levels of IL-6 (−44.2 %) and TNF-α (−42.7 %) (<em>p</em> < 0.01). Mechanistically, Fxyd5 silencing suppressed NF-κB activation, and these protective effects were confirmed in vitro in H/R-treated cardiomyocytes.</div></div><div><h3>Conclusion</h3><div>Fxyd5 silencing significantly attenuated I/R-induced myocardial injury, reduced infarct size, and improved cardiac function, while also decreasing apoptosis and inflammatory cytokine expression (<em>p</em> < 0.01). These findings indicate that Fxyd5 contributes to the pathogenesis of myocardial I/R injury and that its inhibition confers cardioprotective effects, partly through suppression of the NF-κB pathway.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"93 ","pages":"Article 102282"},"PeriodicalIF":1.4000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplant immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0966327425001108","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Myocardial ischemia/reperfusion (I/R) injury is a common cause of death. FXYD domain-containing ion transport regulator-5 (Fxyd5) is a type I membrane protein that plays a significant role in mediating cellular functions. However, the expression and function of Fxyd5 in myocardial I/R injury remain unclear.

Methods

Male C57BL/6 mice (8–10 weeks) were subjected to myocardial I/R by ligating the left anterior descending coronary artery. Preventive intervention was performed using adeno-associated virus 9 (AAV9)-mediated Fxyd5 knockdown. An in vitro hypoxia/reoxygenation (H/R) in H9c2 cardiomyoblasts was used for validation.

Results

Myocardial I/R injury significantly upregulated Fxyd5 expression (p < 0.01). Silencing Fxyd5 markedly improved cardiac function, as evidenced by a 58.0 % increase in EF (p < 0.01) and a 54.5 % reduction in infarct size (p < 0.01). Fxyd5 knockdown also attenuated myocardial apoptosis and inflammation, demonstrated by decreased cleaved caspase-3 expression and reduced levels of IL-6 (−44.2 %) and TNF-α (−42.7 %) (p < 0.01). Mechanistically, Fxyd5 silencing suppressed NF-κB activation, and these protective effects were confirmed in vitro in H/R-treated cardiomyocytes.

Conclusion

Fxyd5 silencing significantly attenuated I/R-induced myocardial injury, reduced infarct size, and improved cardiac function, while also decreasing apoptosis and inflammatory cytokine expression (p < 0.01). These findings indicate that Fxyd5 contributes to the pathogenesis of myocardial I/R injury and that its inhibition confers cardioprotective effects, partly through suppression of the NF-κB pathway.

查看原文本刊更多论文

Fxyd5下调通过抑制心肌炎症保护心脏免受缺血/再灌注损伤。

背景：心肌缺血/再灌注（I/R）损伤是常见的死亡原因。FXYD结构域离子运输调节因子-5 （Fxyd5）是一种I型膜蛋白，在调节细胞功能中起重要作用。然而，Fxyd5在心肌I/R损伤中的表达和功能尚不清楚。方法：雄性C57BL/6小鼠（8 ~ 10 周）结扎左冠状动脉前降支进行心肌I/R。采用腺相关病毒9 （AAV9）介导的Fxyd5敲低进行预防性干预。采用体外缺氧/再氧化（H/R）法对H9c2型心肌细胞进行验证。结果：心肌I/R损伤可显著上调Fxyd5的表达（p ）结论：Fxyd5沉默可显著减轻I/R诱导的心肌损伤，减少梗死面积，改善心功能，同时减少细胞凋亡和炎症细胞因子的表达(p

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Transplant immunology 医学-免疫学

CiteScore

2.10

自引率

13.30%

发文量

198

审稿时长

48 days

期刊介绍： Transplant Immunology will publish up-to-date information on all aspects of the broad field it encompasses. The journal will be directed at (basic) scientists, tissue typers, transplant physicians and surgeons, and research and data on all immunological aspects of organ-, tissue- and (haematopoietic) stem cell transplantation are of potential interest to the readers of Transplant Immunology. Original papers, Review articles and Hypotheses will be considered for publication and submitted manuscripts will be rapidly peer-reviewed and published. They will be judged on the basis of scientific merit, originality, timeliness and quality.