特发性二尖瓣腱索断裂的分子机制：转录组分析与炎症评估的见解

Molecular Mechanisms in Idiopathic Mitral Valve Chordae Tendineae Rupture: Insights from Transcriptome Analysis and Inflammation Evaluation.

作者信息

Wang Qiuji, Zhong Lishan, Hua Linbin, Pang Shanwen, Li Yuxin, Zhang Zhaolong, Zhao Junfei, Huang Huanlei

机构信息

Department of Cardiac Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People's Republic of China.

Guangdong Cardiovascular Institute, Guangzhou, 510030, People's Republic of China.

出版信息

J Inflamm Res. 2025 Apr 5;18:4771-4783. doi: 10.2147/JIR.S510525. eCollection 2025.

DOI:10.2147/JIR.S510525

PMID:40206810

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11980926/

Abstract

OBJECTIVE

This study investigates the molecular mechanisms and hub genes in idiopathic rupture of mitral valve chordae tendineae (iRCT).

METHODS

Histological changes were assessed via pathological staining, and transcriptome sequencing was performed on samples from 8 iRCT patients and 6 controls. Differentially expressed genes (DEGs), functional enrichment, PPI networks, and immune cell infiltration were analyzed. Hub gene expression was validated using RT-qPCR.

RESULTS

iRCT samples exhibited cell proliferation, disorganized collagen fibers, and elastin fiber rupture. Immunohistochemical analysis further confirmed that activated fibroblasts, macrophages, dendritic cells, and T cells were increased in iRCT samples compared to normal samples. Additionally, iRCT samples exhibited an increased content of collagen fibers and elastin fibers. Transcriptome analysis identified 208 DEGs (109 upregulated, 99 downregulated) linked to inflammation, immune activation, and extracellular matrix remodeling.

CONCLUSION

iRCT involves ECM remodeling, inflammation, and immune dysregulation, with identified hub genes offering potential therapeutic targets.

摘要

目的

本研究探讨特发性二尖瓣腱索断裂（iRCT）的分子机制和关键基因。

方法

通过病理染色评估组织学变化，并对8例iRCT患者和6例对照的样本进行转录组测序。分析差异表达基因（DEG）、功能富集、蛋白质-蛋白质相互作用（PPI）网络和免疫细胞浸润。使用逆转录定量聚合酶链反应（RT-qPCR）验证关键基因表达。

结果

iRCT样本表现出细胞增殖、胶原纤维排列紊乱和弹性纤维断裂。免疫组织化学分析进一步证实，与正常样本相比，iRCT样本中活化的成纤维细胞、巨噬细胞、树突状细胞和T细胞增加。此外，iRCT样本中胶原纤维和弹性纤维含量增加。转录组分析确定了208个与炎症、免疫激活和细胞外基质重塑相关的DEG（109个上调，99个下调）。