Exploration of Clozapine-Induced Cardiomyopathy and Its Mechanism.

IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiovascular Toxicology Pub Date : 2024-11-01 Epub Date: 2024-08-17 DOI:10.1007/s12012-024-09909-7
Shangyu Zhang, Pengyue Jin, Li Yang, Yujie Zeng, Yongguo Li, Renkuan Tang
{"title":"Exploration of Clozapine-Induced Cardiomyopathy and Its Mechanism.","authors":"Shangyu Zhang, Pengyue Jin, Li Yang, Yujie Zeng, Yongguo Li, Renkuan Tang","doi":"10.1007/s12012-024-09909-7","DOIUrl":null,"url":null,"abstract":"<p><p>In this study, by pooling the clinical data of patients who died with a history of long-term clozapine use and by examining their hearts, it was found that long-term clozapine use can lead to cardiomyopathy and that its presentation resembles arrhythmogenic cardiomyopathy (ACM), i.e., it exhibits a predominantly right ventricular fatty infiltration with mild left ventricular damage. The transcriptomic data of rat cardiomyocytes after clozapine intervention were analyzed by transcriptomic approach to explore the causes of clozapine cardiomyopathy. The cause of clozapine cardiomyopathy was then explored by a transcriptomic approach, which revealed that its clozapine action on cardiomyocytes enriched cardiomyocyte-related differential genes in biological processes such as muscle development and response to hypoxia, as well as pathways such as fatty acid metabolism and cellular autophagy. Transcriptomic analysis showed that Egr1, Egr2, ler2, Jun, Mapk9, Nr1d2, Atf3, Bhlhe40, Crem, Cry1, Cry2, Dbp were hub genes for clozapine injury to the myocardium, and that these genes may play an important role in the myocardial ACM-like changes caused by clozapine. Combined with the results of pathological examination and transcriptomic analysis, it can be concluded that the long-term action of clozapine on cardiomyocytes leads to cellular autophagy and subsequent structural remodeling of the heart, and in the remodeling affects fatty acid metabolism, which eventually leads to ACM-like changes.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12012-024-09909-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/17 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0

Abstract

In this study, by pooling the clinical data of patients who died with a history of long-term clozapine use and by examining their hearts, it was found that long-term clozapine use can lead to cardiomyopathy and that its presentation resembles arrhythmogenic cardiomyopathy (ACM), i.e., it exhibits a predominantly right ventricular fatty infiltration with mild left ventricular damage. The transcriptomic data of rat cardiomyocytes after clozapine intervention were analyzed by transcriptomic approach to explore the causes of clozapine cardiomyopathy. The cause of clozapine cardiomyopathy was then explored by a transcriptomic approach, which revealed that its clozapine action on cardiomyocytes enriched cardiomyocyte-related differential genes in biological processes such as muscle development and response to hypoxia, as well as pathways such as fatty acid metabolism and cellular autophagy. Transcriptomic analysis showed that Egr1, Egr2, ler2, Jun, Mapk9, Nr1d2, Atf3, Bhlhe40, Crem, Cry1, Cry2, Dbp were hub genes for clozapine injury to the myocardium, and that these genes may play an important role in the myocardial ACM-like changes caused by clozapine. Combined with the results of pathological examination and transcriptomic analysis, it can be concluded that the long-term action of clozapine on cardiomyocytes leads to cellular autophagy and subsequent structural remodeling of the heart, and in the remodeling affects fatty acid metabolism, which eventually leads to ACM-like changes.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
探索氯氮平诱发心肌病及其机制
在这项研究中,通过汇集有长期服用氯氮平病史的死亡患者的临床数据,并通过检查他们的心脏,发现长期服用氯氮平可导致心肌病,其表现类似于心律失常性心肌病(ACM),即主要表现为右心室脂肪浸润,左心室轻度损伤。通过转录组学方法分析了氯氮平干预后大鼠心肌细胞的转录组数据,以探索氯氮平心肌病的病因。随后,通过转录组学方法探讨了氯氮平心肌病的病因,发现氯氮平对心肌细胞的作用富集了心肌细胞相关的差异基因,这些差异基因涉及肌肉发育、缺氧反应等生物过程,以及脂肪酸代谢和细胞自噬等通路。转录组分析表明,Egr1、Egr2、ler2、Jun、Mapk9、Nr1d2、Atf3、Bhlhe40、Crem、Cry1、Cry2、Dbp是氯氮平损伤心肌的枢纽基因,这些基因可能在氯氮平引起的心肌ACM样变中发挥重要作用。结合病理检查和转录组学分析结果,可以得出结论:氯氮平对心肌细胞的长期作用导致细胞自噬,进而导致心脏结构重塑,在重塑过程中影响脂肪酸代谢,最终导致ACM样变。
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 去求助
来源期刊
Cardiovascular Toxicology
Cardiovascular Toxicology 医学-毒理学
CiteScore
6.60
自引率
3.10%
发文量
61
审稿时长
>12 weeks
期刊介绍: Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.
期刊最新文献
Correction: Novel Insights into Causal Effects of Serum Lipids and Apolipoproteins on Cardiovascular Morpho-Functional Phenotypes. Persistent Ferroptosis Modulates Cardiac Remodeling and M2 Macrophage Polarization, Which Can be Mitigated by Astaxanthin During Myocardial Infarction Recovery. Small Molecules Targeting Mitochondria: A Mechanistic Approach to Combating Doxorubicin-Induced Cardiotoxicity. Myocarditis Following Pembrolizumab Plus Axitinib, and Belzutifan Plus Lenvatinib for Renal Cell Carcinoma: A Case Report. Sevoflurane Affects Myocardial Autophagy Levels After Myocardial Ischemia Reperfusion Injury via the microRNA-542-3p/ADAM9 Axis.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1