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Updated: Jul 2, 2026
03:45
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Proteogenomics of Hypertrophic Cardiomyopathy Reveals Subtype-Specific Therapy
Ke Ma1,2, Jie Yang1,2, Hongchang Guo1
1Beijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).
Circulation Research
|July 1, 2026
Summary
This study identified two molecular subtypes of hypertrophic cardiomyopathy (HCM) based on proteogenomics, revealing metabolic differences and enabling targeted therapies for severe HCM patients.
Area of Science:
- Cardiovascular Biology
- Genomics
- Proteomics
- Metabolomics
Background:
- Hypertrophic cardiomyopathy (HCM) is a complex genetic heart disease with variable patient outcomes.
- Current understanding of HCM mechanisms is limited, hindering effective risk stratification and treatment.
- This study addresses the need for molecular insights into HCM heterogeneity.
Purpose of the Study:
- To identify molecular subtypes of HCM using integrated proteogenomic analysis.
- To explore subtype-specific therapeutic strategies for improved patient outcomes.
- To elucidate the causal link between molecular pathways and HCM pathogenesis.
Main Methods:
- Integrated proteogenomic analysis of 132 HCM patient myocardial samples (whole-exome sequencing, RNA sequencing, proteomics).
- Unsupervised clustering to define HCM subtypes, validated in independent cohorts and cellular models.
- In silico drug screening and in vitro/in vivo validation of subtype-specific therapeutic interventions.
Main Results:
- Two proteome-based HCM subtypes identified: severe and mild, with distinct clinical characteristics and prognoses.
- Severe HCM subtype predominantly driven by impaired fatty acid metabolism and oxidative phosphorylation.
- Genetic evidence confirmed a causal link between reduced fatty acid oxidation and HCM; Baicalin showed therapeutic potential.
Conclusions:
- Integrated proteogenomics reveals significant metabolic heterogeneity in HCM.
- Identified molecular subtypes allow for improved risk stratification.
- Subtype-specific therapeutic strategies, like Baicalin for severe HCM, offer new treatment avenues.
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