GDF11 alleviates cardiac ischemia/reperfusion injury by suppressing the mtDNA damage-inflammatory response axis

IF 4.2 3区医学 Q1 PHARMACOLOGY & PHARMACY

European journal of pharmacology Pub Date : 2025-02-15 DOI:10.1016/j.ejphar.2025.177392

Dan Zhao , Zihui Wang , Yanyan Chen , Zhiwei Wang , Wei Shi , Lijie Zhang , Yinxiang Wei , Shulian Li , Xianjie Zheng , Guoliang Wang , Yaohui Wang

{"title":"GDF11 alleviates cardiac ischemia/reperfusion injury by suppressing the mtDNA damage-inflammatory response axis","authors":"Dan Zhao , Zihui Wang , Yanyan Chen , Zhiwei Wang , Wei Shi , Lijie Zhang , Yinxiang Wei , Shulian Li , Xianjie Zheng , Guoliang Wang , Yaohui Wang","doi":"10.1016/j.ejphar.2025.177392","DOIUrl":null,"url":null,"abstract":"<div><div>Growth differentiation factor 11 (GDF11) has been reported to play a protective role in myocardial infarction. Mitochondrial DNA (mtDNA) damage is one of the pivotal factors in the initiation of myocardial cell damage. However, whether GDF11 can ameliorate mtDNA damage through its cardioprotective effect remains largely unknown. In this study, we obtained the GDF11-Fc fusion protein from mammalian cells and evaluated its cardioprotective effect in a mouse myocardial infarction model by TTC-Evans blue staining and morphological and enzymatic detection. Similar protective effects were observed in H9C2 cells and NRVMs. Mechanistically, we found that mtDNA damage was increased in I/R hearts. Exogenous administration of GDF11-Fc alleviated mtDNA damage and subsequent NLRP3 inflammasome activity, possibly through a reduction in ROS. In conclusion, GDF11 can ameliorate myocardial ischemia-reperfusion injury by inhibiting the inflammatory response induced by mtDNA damage.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"993 ","pages":"Article 177392"},"PeriodicalIF":4.2000,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014299925001463","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Growth differentiation factor 11 (GDF11) has been reported to play a protective role in myocardial infarction. Mitochondrial DNA (mtDNA) damage is one of the pivotal factors in the initiation of myocardial cell damage. However, whether GDF11 can ameliorate mtDNA damage through its cardioprotective effect remains largely unknown. In this study, we obtained the GDF11-Fc fusion protein from mammalian cells and evaluated its cardioprotective effect in a mouse myocardial infarction model by TTC-Evans blue staining and morphological and enzymatic detection. Similar protective effects were observed in H9C2 cells and NRVMs. Mechanistically, we found that mtDNA damage was increased in I/R hearts. Exogenous administration of GDF11-Fc alleviated mtDNA damage and subsequent NLRP3 inflammasome activity, possibly through a reduction in ROS. In conclusion, GDF11 can ameliorate myocardial ischemia-reperfusion injury by inhibiting the inflammatory response induced by mtDNA damage.

Abstract Image

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

European journal of pharmacology 医学-药学

CiteScore

9.00

自引率

0.00%

发文量

572

审稿时长

34 days

期刊介绍： The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems. The scope includes: Behavioural pharmacology Neuropharmacology and analgesia Cardiovascular pharmacology Pulmonary, gastrointestinal and urogenital pharmacology Endocrine pharmacology Immunopharmacology and inflammation Molecular and cellular pharmacology Regenerative pharmacology Biologicals and biotherapeutics Translational pharmacology Nutriceutical pharmacology.