Related Experiment Video
Updated: Feb 7, 2026
03:45
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
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Cross-dataset transcriptomic analyses identify a conserved ENPP2+ macrophage-fibroblast activation axis in
Fanyi Huang1, Mi Zhou2, Yanjia Chen1
1Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.
Briefings in Bioinformatics
|February 5, 2026
Summary
Hypertrophic cardiomyopathy (HCM) involves myocardial fibrosis. This study reveals pro-inflammatory macrophages drive fibroblast activation via ENPP2, leading to COL14A1 secretion and fibrosis, offering new therapeutic targets.
Area of Science:
- Cardiovascular Biology
- Molecular Pathology
- Genomics
Background:
- Hypertrophic cardiomyopathy (HCM) is linked to myocardial fibrosis, a key factor in sudden cardiac death risk.
- Existing research notes fibroblast activation in HCM but lacks detailed regulatory mechanism insights.
Purpose of the Study:
- To elucidate the molecular mechanisms driving myocardial fibrosis in hypertrophic cardiomyopathy.
- To identify key cellular players and signaling pathways involved in HCM pathogenesis.
Main Methods:
- Analysis of single-nucleus sequencing (snRNA-seq) and spatial transcriptomics datasets from HCM patients.
- Validation through histopathological and molecular biology experiments.
Main Results:
- Identified a phenotypic transformation of macrophages in HCM, characterized by high ENPP2 expression.
- Demonstrated that these macrophages promote fibroblast activation, potentially via lysophosphatidic acid.
- Found activated fibroblasts secrete COL14A1, a major contributor to myocardial fibrosis.
Conclusions:
- Macrophage reprogramming and subsequent fibroblast activation are central to myocardial fibrosis in HCM.
- ENPP2 and COL14A1 represent potential therapeutic targets for HCM.
- Findings suggest universal applicability across different genetic HCM backgrounds.
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