ArticleCirculation. Genomic and precision medicine2024
Integrating Clinical Phenotype With Multiomics Analyses of Human Cardiac Tissue Unveils Divergent Metabolic Remodeling in Genotype-Positive and Genotype-Negative Patients With Hypertrophic Cardiomyopathy.
Article in Circulation. Genomic and precision medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Effect of trimetazidine dihydrochloride therapy on myocardial external efficiency in pre-clinical individuals with a hypertrophic cardiomyopathy pathogenic variant: results of the ENERGY trial.Cardiovascular research · 2025Trial
- Combined Lipidomic and Metabolomic Analyses on Cardiac Organoids.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Multiple triggering mechanisms of myocardial fibrosis: Comparison and integration in different disease contexts.iScience · 2026Review
- Changes in cardiac myosin acetylation disrupt the super-relaxed state in genotype-negative hypertrophic cardiomyopathy with type 2 diabetes.Cardiovascular diabetology · 2026Article
- Choice of cardioplegia influences metabolomics of human cardiac tissue.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- 2026 Expert Consensus Recommendations on Hypertrophic Cardiomyopathy: A Report of the Task Force of the Taiwan Society of Cardiology.Acta Cardiologica Sinica · 2026Article
- Early fibrotic gene activation precedes structural remodeling in the heart of cardiac myosin binding protein-C knockout mice.Physiological genomics · 2026Article
- Article
- Abnormal Lipid Signaling Characterizes Diastolic Dysfunction in Pediatric Cardiomyopathy.JACC. Basic to translational science · 2026Article
- Sex- and Exercise-Dependent Modulation of Hypertrophic Remodeling by the MCT1 rs1049434 Polymorphism.Genes · 2026Article
- Article
- Signaling pathway alterations in hearts of a porcine model harboring a β-myosin heavy chain (MYH7-R403Q) gene variant.Journal of molecular and cellular cardiology plus · 2025Article
- A combined genomic arrhythmia propensity score delineates cumulative risk.Cell reports. Medicine · 2025Article
- Metabolic cardiomyopathies: untangling clinical heterogeneity with human stem-cell derived models.EMBO molecular medicine · 2025Review
- Heterogeneous Dysregulation of Myosin Super-Relaxation and Energetics in Hypertrophic Cardiomyopathy.Circulation. Heart failure · 2025Article
- Ceramides in cardiovascular disease: emerging role as independent risk predictors and novel therapeutic targets.Cardiovascular research · 2025Review
- Experimental Models of Hypertrophic Cardiomyopathy: A Systematic Review.JACC. Basic to translational science · 2025Review
- Identification of biomarkers associated with energy metabolism in hypertrophic cardiomyopathy and exploration of potential mechanisms of roles.Frontiers in cardiovascular medicine · 2025Article
- Mechanisms of metabolic transition in hypertrophic cardiomyopathy.Frontiers in physiology · 2025Review
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypertrophic cardiomyopathy (HCM) is caused by sarcomere gene mutations (genotype-positive HCM) in ≈50% of patients and occurs in the absence of mutations (genotype-negative HCM) in the other half of patients. We explored how alterations in the metabolomic and lipidomic landscape are involved in cardiac remodeling in both patient groups.
methodsWe performed proteomics, metabolomics, and lipidomics on myectomy samples (genotype-positive N=19; genotype-negative N=22; and genotype unknown N=6) from clinically well-phenotyped patients with HCM and on cardiac tissue samples from sex- and age-matched and body mass index-matched nonfailing donors (N=20). These data sets were integrated to comprehensively map changes in lipid-handling and energy metabolism pathways. By linking metabolomic and lipidomic data to variability in clinical data, we explored patient group-specific associations between cardiac and metabolic remodeling.
resultsHCM myectomy samples exhibited (1) increased glucose and glycogen metabolism, (2) downregulation of fatty acid oxidation, and (3) reduced ceramide formation and lipid storage. In genotype-negative patients, septal hypertrophy and diastolic dysfunction correlated with lowering of acylcarnitines, redox metabolites, amino acids, pentose phosphate pathway intermediates, purines, and pyrimidines. In contrast, redox metabolites, amino acids, pentose phosphate pathway intermediates, purines, and pyrimidines were positively associated with septal hypertrophy and diastolic impairment in genotype-positive patients.
conclusionsWe provide novel insights into both general and genotype-specific metabolic changes in HCM. Distinct metabolic alterations underlie cardiac disease progression in genotype-negative and genotype-positive patients with HCM.
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