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Updated: Jun 14, 2025

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Proteomic Characterisation of Heart Failure Reveals a Unique Molecular Phenotype for Hypertrophic Cardiomyopathy
Claire Tonry1, Katie Linden1, Patrick Collier2
1Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, UK.
Insights
This study compared the molecular profiles of hypertrophic cardiomyopathy (HCM) to other cardiomyopathies. Researchers identified unique proteins and pathways in HCM, offering potential for improved diagnostics and treatments.
Area of Science:
- Cardiology
- Proteomics
- Biochemistry
Background:
- Hypertrophic cardiomyopathy (HCM) presents diagnostic challenges and lacks optimal treatments.
- Understanding the molecular differences between HCM and other cardiomyopathies is crucial.
Purpose of the Study:
- To compare the molecular proteomic profiles of HCM, ischemic cardiomyopathy (ISCM), and dilated cardiomyopathy (DCM).
- To identify novel protein and pathway targets for improved HCM diagnostics and therapeutics.
Main Methods:
- Utilized high-throughput mass spectrometry for deep quantitative proteomic analysis of left ventricular myocardial tissue.
- Analyzed tissue from HCM, DCM, ISCM, and non-heart-failure control patients.
Main Results:
- HCM exhibited a distinct proteomic profile compared to DCM and ISCM.
- Identified differentially expressed proteins unique to HCM (fold change ≥1.5 or ≤0.67, q-value ≤0.05).
- Validated significant associations between candidate proteins and HCM clinical features in an independent dataset.
Conclusions:
- This study provides one of the most extensive proteomic datasets for myocardial tissue to date.
- Revealed unique proteomic signatures and disease-relevant pathways in HCM.
- Identified promising, HCM-specific biomarker candidates for potential diagnostic and therapeutic development.
Abstract:
Hypertrophic cardiomyopathy (HCM) is a disease, which is difficult to diagnose at an early stage and for which there is a pressing need for more effective treatment options. The purpose of this study was to compare the molecular profile of HCM to that of ischaemic cardiomyopathy (ISCM) and dilated cardiomyopathy (DCM) for identification of protein and pathway targets that could support the development of better diagnostic and treatment options for HCM. A high-throughput mass spectrometry workflow was applied to achieve deep quantitative coverage of left ventricular tissue from HCM, DCM, ISCM and non-heart-failure control patients. HCM had a diverse proteomic profile compared to that of DCM and ISCM. Differentially expressed proteins unique to HCM were identified based on an observed fold change of ≥1.5 or ≤0.67 and q-value ≤ 0.05. Candidate proteins of interest were found to be significantly associated with clinical features of HCM. The significant association between these proteins and HCM was validated in an independent dataset. This represents one of the largest and deepest proteomic datasets for myocardial tissue reported to date. The dataset highlights the diverse proteomic profile of HCM, relative to other cardiomyopathies, and reveals disease-relevant pathways and promising biomarker candidates that are uniquely associated with HCM.

