Cardiomyopathy and Myosin Studies

Ankyrin-B regulates cardiomyocyte sarcomere organization and its protein-protein interactions are significantly altered by p.S646F expression

This study investigates how ANKB regulates cardiomyocyte sarcomere structure and shows that the p.S646F variant alters its protein interactions, leading to structural abnormalities.

Revisiting the SRX paradox for myosin and myofibrils

The paper re-examines the SRX state in myosin using mant-ATP displacement assays and finds no evidence of the SRX state in isolated myosin but detects two components in myofibrils, suggesting distinct myosin populations in thick filaments.

Motor Occupancy Defines Emergent Mechanical States in Cardiac Myosin Ensembles

This study investigates how motor occupancy affects force generation in cardiac myosin ensembles using drugs to perturb occupancy and optical trapping measurements.

Increased Nuclear Susceptibility to Mechanical Stress in Phospholamban R14del Cardiomyopathy: A New Perspective on Disease Heterogeneity

This study shows that the PLN R14del mutation increases nuclear susceptibility to mechanical stress in cardiomyopathy, linking nuclear dysfunction to disease variability.

Tunable Magnetorheological Elastomer Substrates for Studying Mechano-Genetic Interactions in Hypertrophic Cardiomyopathy

This study uses tunable magnetorheological elastomer substrates to investigate mechano-genetic interactions in HCM by applying dynamic mechanical stress to hiPSC-derived cardiomyocytes with a MYBPC3 mutation.

The E525K β-Myosin Mutation Causes Hypocontractility in Cardiomyocytes Without Altering Crossbridge Cycling

This study shows that the E525K β-myosin mutation reduces cardiomyocyte contraction without altering crossbridge cycling, through structural and computational analysis.

LMNA Haploinsufficiency in Human iPSC-Derived Cardiac Organoids Reveals Early Fibrotic Signaling as a Therapeutically Targetable Process

This study uses cardiac organoids derived from patient iPSCs to show that LMNA haploinsufficiency causes early fibrotic signaling, which can be targeted by antifibrotic drugs.

MAP3K7 Loss of Function Causes Dilated Cardiomyopathy

This paper shows that loss-of-function variants in MAP3K7 cause dilated cardiomyopathy (DCM), both as part of syndromic disease and as apparently isolated DCM.

The Dilated Cardiomyopathy E525K Mutation Stabilizes the Cardiac Myosin Interacting-Heads Motif While Activating the Isolated Motor Domain

This study investigates how the E525K mutation in cardiac myosin affects its structure and function by analyzing conformational changes using cryo-EM and MD simulations.

The molecular structural basis of the braking action of muscle

This study identifies the molecular structural basis of muscle braking, showing it results from both myosin motor conformational changes and filament lattice distortion during stretching.

Missense LMNA Variant Compromises Nuclear Integrity and Sarcomeric Remodeling in Dilated Cardiomyopathy

This study investigates the effects of a missense LMNA variant in DCM patients, showing nuclear integrity and sarcomere remodeling defects in iPSC-derived cardiomyocytes.

Mapping and rewiring the MYBPC3 promoter for rescue of haploinsufficiency driven hypertrophic cardiomyopathy

The paper maps and redesigns the MYBPC3 promoter to enhance expression and treat haploinsufficient hypertrophic cardiomyopathy.

Myotropes unveil two myosin cycles with distinct kinetics and stroke size

The paper uses single-molecule techniques to reveal two distinct myosin cycles with different kinetics and stroke sizes affected by mavacamten and omecamtiv mecarbil.

Transcriptomic analysis of human induced pluripotent stem cell cardiomyocytes and myocardial tissue reveals novel role for miR-9-5p in hypertrophic cardiomyopathy

This study identifies miR-9-5p as a regulator of cardiomyocyte hypertrophy and contractility in HCM using iPSC models and miRNA profiling.

Therapeutic targeting of MYBPC3 mutation-specific hypertrophic cardiomyopathy guided by network modeling

This study identifies mTOR as a therapeutic target for MYBPC3 mutation-induced hypertrophic cardiomyopathy using network modeling and experimental validation.

Patient-Derived hiPSC-Cardiomyocytes and Engineered Heart Tissues Reveal Distinct Functional Phenotypes in Inherited Cardiomyopathies

This study uses patient-derived hiPSC-cardiomyocytes and engineered heart tissues to compare functional and molecular phenotypes in HCM and DCM, revealing genotype-specific responses to stimuli.

Cardiomyocyte prohibitin ablation reprograms cardiac metabolism revealing a pathogenic role for mTORC1 in dilated cardiomyopathy

This study shows that PHB complex ablation in cardiomyocytes leads to mTORC1 activation and metabolic reprogramming, causing dilated cardiomyopathy and mortality in mice.

Optimized Mn2+-Phos-tag Gels Reveal Sarcomeric Protein Dephosphorylation upon Myofibril Preparation

This paper optimizes Mn2+-Phos-tag SDS-PAGE for cardiac myofilament proteins, showing that myofibril preparation causes significant dephosphorylation of MLC2 and cTnI.

The Maine Coon Cat Harboring the MYBPC3-A31P Mutation: A Genotype-Stratified Phenotypic Characterization of Hypertrophic Cardiomyopathy

This study characterizes the phenotypic effects of MYBPC3-A31P mutation in Maine Coon cats, showing gene-dose effects on cardiac structure and function, with homozygous cats exhibiting more severe features.

Histone lysine demethylase inhibition is a disease-modifying therapy for hypertrophic cardiomyopathy

This study shows that inhibiting histone lysine demethylases with JIB-04 prevents and reverses hypertrophic cardiomyopathy through epigenetic changes.

Diffuse generalized phenotype of hypertrophic cardiomyopathy: genetic spectrum and surgical correction

The paper evaluates genetic causes and surgical outcomes in patients with diffuse generalized hypertrophic cardiomyopathy (DG-HCM), finding a 20% prevalence of DG-HCM among obstructive HCM patients and long-term benefits from specific surgical interventions.

The SMYD1 p.Asn101Ser is a partial loss-of-function variant that impairs mitochondrial function and leads to early-onset cardiomyopathy.

This study functionally characterizes a SMYD1 variant linked to early-onset cardiomyopathy, showing it impairs mitochondrial function and leads to disease.

Genotype-Phenotype Correlations Identify Phenotypic Differences in Sarcomere Mutation-Positive Hypertrophic Cardiomyopathy in the NHLBI HCM Registry

The paper identifies phenotypic differences in sarcomere mutation-positive hypertrophic cardiomyopathy using CMR data from the NHLBI HCM Registry, resolving prior discrepancies through meta-analysis.

A highly penetrant LMNA R541C variant associated with dilated cardiomyopathy leads to dysregulation in metabolism and proliferation pathways in stem cell-derived cardiomyocytes

This study identifies a LMNA R541C variant linked to dilated cardiomyopathy and shows it disrupts metabolism and proliferation pathways in stem cell-derived cardiomyocytes.

Deletion of cytoplasmic β/γ-actin in the mouse heart protects from disease by augmenting sarcolemma stability

This study shows deleting cytoplasmic β/γ-actin in mouse hearts improves sarcolemma stability and protects against disease under stress.

Unmasking Supervillin: SVIL haploinsufficiency causes hypertrophic cardiomyopathy by impairing mechanotransduction and cellular energetics.

This study identifies SVIL haploinsufficiency as a cause of hypertrophic cardiomyopathy by impairing mechanotransduction and cellular energetics, with potential therapeutic implications for mitochondrial-targeted treatments.

Pathogenic MYBPC3 missense variants alter protein-protein interactions within the sarcomere

This study identifies pathogenic MYBPC3 missense variants in HCM patients and shows they disrupt protein interactions and alter proximity to thin-filament proteins.

The Ca2+-Sensitivity of Contraction is Increased in the Left Atrium and Left Ventricle of Patients with Ischemic Heart Failure

This study examines changes in calcium sensitivity and contractile properties of left atrial and ventricular myocardium in ischemic heart failure, finding increased calcium sensitivity and altered kinetics in the left atrium.

Load-Dependent Effects of Sodium Glucose Co-Transporter Inhibitors on Work in Human Hypertrophic Cardiomyopathy Living Myocardial Slices.

This study uses human living myocardial slices to examine how sodium glucose co-transporter inhibitors affect myocardial work in hypertrophic cardiomyopathy under varying loading conditions.

Proteomics Uncovers Cryptic JPH2 Loss in Paediatric Dilated Cardiomyopathy

This study uses proteomics to identify a cryptic JPH2 loss-of-function in a paediatric DCM patient, revealing a novel mechanism of recessive disease.