ArticleJournal of the American College of Cardiology2024
Comprehensive Proteomic Profiling of Human Myocardium Reveals Signaling Pathways Dysregulated in Hypertrophic Cardiomyopathy.
Article in Journal of the American College of Cardiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Metabolomic biomarkers and metabolic remodelling in genetically characterised hypertrophic cardiomyopathy: a systematic review.Metabolomics : Official journal of the Metabolomic Society · 2026Pooled it
- Evidence for a role of adverse sarcomere signaling in atrial fibrillation induction.Journal of molecular and cellular cardiology plus · 2026Review
- Reversing the pipeline: a 'human-first' multi-omics approach to cardiovascular discovery.Experimental & molecular medicine · 2026Review
- The ADP-ribosyltransferases 3 (ART3) is a novel suppressor of pathological cardiac hypertrophy by ribosylating ITGA7.Acta pharmaceutica Sinica. B · 2026Article
- Proteogenomics of Hypertrophic Cardiomyopathy Reveals Subtype-Specific Therapy.Circulation research · 2026Observational
- Beta-Adrenergic Stimulation andbioRxiv : the preprint server for biology · 2026Article
- Proteomic profiling identifies molecular subtypes and unveils mechanistic insights into clinical features of hypertrophic cardiomyopathy.Journal of translational medicine · 2026Article
- Titin's P-zone domains A164-167 are essential for thick filament structural arrangement.The Journal of general physiology · 2026Article
- Abnormal Lipid Signaling Characterizes Diastolic Dysfunction in Pediatric Cardiomyopathy.JACC. Basic to translational science · 2026Article
- Cross-dataset transcriptomic analyses identify a conserved ENPP2+ macrophage-fibroblast activation axis in hypertrophic cardiomyopathy.Briefings in bioinformatics · 2026Article
- Molecular Pathology of Cardiomyopathies: Bridging Morphology, Genomics, and Clinical Phenotypes.Current issues in molecular biology · 2026Review
- Global Proteoform Alterations Across Multiple Cellular Compartments Underlie Obstructive Hypertrophic Cardiomyopathy.Circulation. Heart failure · 2025Article
- Fibroblasts Are the Primary Contributors to a Disrupted Micro-Environment in End-Stage Pediatric Hypertrophic Cardiomyopathy.Circulation. Genomic and precision medicine · 2025Article
- HeterozygousJournal of applied physiology (Bethesda, Md. : 1985) · 2025Article
- Comprehensive plasma metabolomics profiling develops diagnostic biomarkers of obstructive hypertrophic cardiomyopathy.Biomarker research · 2025Article
- Pathways to Precision Medicine in Hypertrophic Cardiomyopathy: Opportunities and Challenges in Plasma Proteomics.Circulation. Heart failure · 2025Article
- Integrative multi-omics identifies MEIS3 as a diagnostic biomarker and immune modulator in hypertrophic cardiomyopathy.Frontiers in immunology · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundHypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. Signaling pathways that link genetic sequence variants to clinically overt HCM and progression to severe forms of HCM remain unknown.
objectivesThe purpose of this study was to identify signaling pathways that are differentially regulated in HCM, using proteomic profiling of human myocardium, confirmed with transcriptomic profiling.
methodsIn this multicenter case-control study, myocardial samples were obtained from cases with HCM and control subjects with nonfailing hearts. Proteomic profiling of 7,289 proteins from myocardial samples was performed using the SomaScan assay (SomaLogic). Pathway analysis of differentially expressed proteins was performed, using a false discovery rate <0.05. Pathway analysis of proteins whose concentrations correlated with clinical indicators of severe HCM (eg, reduced left ventricular ejection fraction, atrial fibrillation, and ventricular tachyarrhythmias) was also executed. Confirmatory analysis of differentially expressed genes was performed using myocardial transcriptomic profiling.
resultsThe study included 99 HCM cases and 15 control subjects. Pathway analysis of differentially expressed proteins revealed dysregulation of the Ras-mitogen-activated protein kinase, ubiquitin-mediated proteolysis, angiogenesis-related (eg, hypoxia-inducible factor-1, vascular endothelial growth factor), and Hippo pathways. Pathways known to be dysregulated in HCM, including metabolic, inflammatory, and extracellular matrix pathways, were also dysregulated. Pathway analysis of proteins associated with clinical indicators of severe HCM and of differentially expressed genes supported these findings.
conclusionsThe present study represents the most comprehensive (>7,000 proteins) and largest-scale (n = 99 HCM cases) proteomic profiling of human HCM myocardium to date. Proteomic profiling and confirmatory transcriptomic profiling elucidate dysregulation of both newly recognized (eg, Ras-mitogen-activated protein kinase) and known pathways associated with pathogenesis and progression to severe forms of HCM.
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