基于铁死亡和免疫异质性鉴定扩张型心肌病的新型治疗靶点
Identification of Novel Targets for Treatment of Dilated Cardiomyopathy Based on the Ferroptosis and Immune Heterogeneity.
作者信息
Lu Hongyu, Xie Yun, Zhou Ziyou, Hong Peijian, Chen Jiyan
机构信息
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People's Republic of China.
出版信息
J Inflamm Res. 2023 Jun 13;16:2461-2476. doi: 10.2147/JIR.S407588. eCollection 2023.
PURPOSE
This study aimed to investigate the role of ferroptosis in dilated cardiomyopathy (DCM) and to identify new targets for treatment and diagnosis of DCM.
METHODS
GSE116250 and GSE145154 were downloaded from the Gene Expression Omnibus database. Unsupervised consensus clustering of DCM patients was used to confirm the impact of ferroptosis. Ferroptosis-related hub genes were identified by WGCNA and single cell sequencing analyses. Finally, we established a DCM mouse model via injection of Doxorubicin to verify the expression level of and colocalization between cell markers and in DCM mouse heart.
RESULTS
A total of 13 ferroptosis-related differentially expressed genes (DEGs) were identified. The DCM patients were divided into two clusters according to the expression of 13 DEGs. The DCM patients in different clusters showed discrepancies in immune infiltration. Four hub genes were further identified by WGCNA analysis. Single cell data analysis revealed that may regulate B cells and DC cells and then participate in immune infiltration discrepancy. The upregulation of and the colocalization of with CD19 (B cell maker) and CD11c (DCs markers) markers were confirmed in DCM mouse hearts.
CONCLUSION
Ferroptosis and the immune microenvironment are closely associated with DCM, and may play an important role through B cells and DCs.
目的
本研究旨在探讨铁死亡在扩张型心肌病（DCM）中的作用，并确定DCM治疗和诊断的新靶点。
方法
从基因表达综合数据库下载GSE116250和GSE145154。对DCM患者进行无监督一致性聚类以确认铁死亡的影响。通过加权基因共表达网络分析（WGCNA）和单细胞测序分析确定铁死亡相关的枢纽基因。最后，我们通过注射阿霉素建立DCM小鼠模型，以验证DCM小鼠心脏中相关基因的表达水平以及细胞标志物之间的共定位情况。
结果
共鉴定出13个与铁死亡相关的差异表达基因（DEGs）。根据13个DEGs的表达将DCM患者分为两个聚类。不同聚类中的DCM患者在免疫浸润方面存在差异。通过WGCNA分析进一步鉴定出4个枢纽基因。单细胞数据分析显示，某基因可能调节B细胞和树突状细胞（DC细胞），进而参与免疫浸润差异。在DCM小鼠心脏中证实了某基因的上调以及该基因与CD19（B细胞标志物）和CD11c（DC细胞标志物）标志物的共定位。
结论
铁死亡和免疫微环境与DCM密切相关，某基因可能通过B细胞和DC细胞发挥重要作用。
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