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Multi-Omics Profiling of Hypertrophic Cardiomyopathy Reveals Altered Mechanisms in Mitochondrial Dynamics and Excitation-Contraction Coupling. 2023

Jarrod Moore, and Jourdan Ewoldt, and Gabriela Venturini, and Alexandre C Pereira, and Kallyandra Padilha, and Matthew Lawton, and Weiwei Lin, and Raghuveera Goel, and Ivan Luptak, and Valentina Perissi, and Christine E Seidman, and Jonathan Seidman, and Michael T Chin, and Christopher Chen, and Andrew Emili
Center for Network Systems Biology, Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

Hypertrophic cardiomyopathy is one of the most common inherited cardiomyopathies and a leading cause of sudden cardiac death in young adults. Despite profound insights into the genetics, there is imperfect correlation between mutation and clinical prognosis, suggesting complex molecular cascades driving pathogenesis. To investigate this, we performed an integrated quantitative multi-omics (proteomic, phosphoproteomic, and metabolomic) analysis to illuminate the early and direct consequences of mutations in myosin heavy chain in engineered human induced pluripotent stem-cell-derived cardiomyocytes relative to late-stage disease using patient myectomies. We captured hundreds of differential features, which map to distinct molecular mechanisms modulating mitochondrial homeostasis at the earliest stages of pathobiology, as well as stage-specific metabolic and excitation-coupling maladaptation. Collectively, this study fills in gaps from previous studies by expanding knowledge of the initial responses to mutations that protect cells against the early stress prior to contractile dysfunction and overt disease.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D002312 Cardiomyopathy, Hypertrophic A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY). Cardiomyopathy, Hypertrophic Obstructive,Cardiomyopathies, Hypertrophic,Cardiomyopathies, Hypertrophic Obstructive,Hypertrophic Cardiomyopathies,Hypertrophic Cardiomyopathy,Hypertrophic Obstructive Cardiomyopathies,Hypertrophic Obstructive Cardiomyopathy,Obstructive Cardiomyopathies, Hypertrophic,Obstructive Cardiomyopathy, Hypertrophic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000095028 Multiomics The study of a variety of data sets, such as TRANSCRIPTOME; PROTEOME; METABOLOME; or MICROBIOME, that are generated from the same biological source, like a cell type or organ, during normal versus diseased states, or other comparable instances. Integrative Omics,Integrative-Omics,Multi-Omics,Pan-Omics,Panomics,Multi Omics,Multi-Omic,Omics, Integrative,Pan Omics
D055815 Young Adult A person between 19 and 24 years of age. Adult, Young,Adults, Young,Young Adults
D057026 Induced Pluripotent Stem Cells Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS. Human Induced Pluripotent Stem Cell,IPS Cell,IPS Cells,Induced Pluripotent Stem Cell,Fibroblast-Derived IPS Cells,Fibroblast-Derived Induced Pluripotent Stem Cells,Human Induced Pluripotent Stem Cells,hiPSC,Cell, Fibroblast-Derived IPS,Cell, IPS,Cells, Fibroblast-Derived IPS,Cells, IPS,Fibroblast Derived IPS Cells,Fibroblast Derived Induced Pluripotent Stem Cells,Fibroblast-Derived IPS Cell,IPS Cell, Fibroblast-Derived,IPS Cells, Fibroblast-Derived
D032383 Myocytes, Cardiac Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC). Cardiomyocytes,Muscle Cells, Cardiac,Muscle Cells, Heart,Cardiac Muscle Cell,Cardiac Muscle Cells,Cardiac Myocyte,Cardiac Myocytes,Cardiomyocyte,Cell, Cardiac Muscle,Cell, Heart Muscle,Cells, Cardiac Muscle,Cells, Heart Muscle,Heart Muscle Cell,Heart Muscle Cells,Muscle Cell, Cardiac,Muscle Cell, Heart,Myocyte, Cardiac
D040901 Proteomics The systematic study of the complete complement of proteins (PROTEOME) of organisms. Peptidomics
D063154 Mitochondrial Dynamics The continuous remodeling of MITOCHONDRIA shape by fission and fusion in response to physiological conditions. Mitochondrial Fission,Mitochondrial Fission and Fusion,Mitochondrial Fusion,Mitochondrial Fusion and Fission,Dynamic, Mitochondrial,Dynamics, Mitochondrial,Fission, Mitochondrial,Fissions, Mitochondrial,Fusion, Mitochondrial,Fusions, Mitochondrial,Mitochondrial Dynamic,Mitochondrial Fissions,Mitochondrial Fusions

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