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

Qiuji Wang,1– 3,* Lishan Zhong,1,2,* Linbin Hua,1– 3 Shanwen Pang,1– 3 Yuxin Li,1,2 Zhaolong Zhang,1,2 Junfei Zhao,1,2 Huanlei Huang1– 3 1Department of Cardiac Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 2Guangdong Cardiovascular Institute, Guangzhou, 510030, People’s Republic of China; 3Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huanlei Huang, Department of Cardiac Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Second Road, Yuexiu District, Guangzhou, Guangdong, People’s Republic of China, Email [email protected] Junfei Zhao, Department of Cardiac Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Second Road, Yuexiu District, Guangzhou, Guangdong, People’s Republic of China, Email [email protected]: 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.Keywords: mitral valve prolapse, chordae tendineae rupture, inflammation, immune response, transcriptome, bioinformatics