Related Experiment Video
Updated: Jun 10, 2026
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Identification of Centrosome Duplication-Related Biomarkers in Hypertrophic Cardiomyopathy Through Integrative
Huigan Li1, Weihua Liu2, Xun Huang2
1Department of Medical Genetics, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University Nanchang Jiangxi China.
Insights
Centrosome duplication genes are linked to hypertrophic cardiomyopathy (HCM). VPS8, a key regulator, impacts cardiomyocyte function and may be a therapeutic target for HCM.
Area of Science:
- Cardiovascular Genetics
- Cell Biology
- Molecular Medicine
Background:
- Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease.
- The role of centrosome duplication genes in HCM pathogenesis is not well understood.
Purpose of the Study:
- To identify centrosome duplication-related genes associated with HCM.
- To investigate the functional role of candidate genes in cardiac cells.
Main Methods:
- Integrative multi-omics analysis including differential expression, WGCNA, and Mendelian randomization.
- Machine learning models and single-cell RNA sequencing.
- In vitro functional assays in cardiomyocytes.
Main Results:
- Two candidate genes, HBEGF and VPS8, showed significant association with HCM.
- VPS8 is highly expressed in cardiomyocytes and dendritic cells.
- VPS8 knockdown impaired cardiomyocyte proliferation, increased apoptosis, and affected structural proteins.
Conclusions:
- Dysregulation of centrosome duplication genes is implicated in HCM.
- VPS8 is identified as a key regulator linking cellular homeostasis and cardiac remodeling.
- VPS8 shows potential as a biomarker and therapeutic target for HCM.
Background:
Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiovascular disorder characterized by ventricular wall thickening and myocardial fibrosis. Centrosome duplication-related gene play critical roles in cell cycle regulation, microtubule organization, and cellular structural homeostasis; however, their mechanistic involvement in HCM remains unclear.
Methods:
An integrative multi-omics strategy was used, incorporating differential expression analysis, weighted gene co-expression network analysis, Mendelian randomization), and multiple machine-learning models to identify centrosome duplication-related genes associated with HCM. Single-cell RNA sequencing was used to assess cell-type-specific expression patterns, followed by in vitro functional assays in cardiomyocytes.
Results:
Two candidate biomarkers, HBEGF and VPS8, were significantly associated with HCM across multiple data sets. Single-cell transcriptomic analysis revealed high VPS8 expression in cardiomyocytes and dendritic cells. Functional assays show that VPS8 knockdown suppressed cardiomyocyte proliferation, increased apoptosis, and reduced the expression of proteins involved in centrosome and microtubule organization, suggesting its involvement in structural maintenance and cell cycle regulation.
Conclusions:
This study suggests a potential association between centrosome duplication-related gene dysregulation and HCM pathogenesis and identifies VPS8 as a key regulator bridging endosomal-lysosomal homeostasis and immune-related remodeling. VPS8 may represent a candidate biomarker and a potential therapeutic target for early diagnosis and intervention in HCM.
