Effect of plasma exosome lncRNA on isoproterenol hydrochloride-induced cardiotoxicity in rats

• Published in: Toxicology and applied pharmacology 2024-03, Vol.484, p.116840-116840, Article 116840
• Main Authors: Zhao, Liyuan, Shi, Lei, Yang, Zixuan, Zheng, Minhui, Sun, Zhimin, Sun, Luyao, Gu, Mengyun, Song, Xin, Liu, Gang, Miao, Feng, Wang, Ming, Zheng, Shaoqiu, Zhang, Peng, Tang, Naping, Liu, Kelan
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers; Cardiotoxicity; Exosomes; Exosomes - genetics; Exosomes - metabolism; Gene Regulatory Networks; Isoproterenol - toxicity; Isoproterenol Hydrochloride; LncRNA; Rats; Rats, Sprague-Dawley; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - metabolism
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2024.116840

Isoprenaline hydrochloride (IH) is a β-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague–Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity. •LncRNA as a novel biomarker of cardiotoxicity.•IH changed the lncRNA expression profile in rat myocardium.•LncRNA mediates signal pathways related to myocardial injury.•Correlation between lncRNA-mRNA-miRNA axis and myocardial injury.