Cardiomyopathy and Myosin Studies

Desmoglein-2 deficiency results in cardiac dysfunction by compromising both Z-disc- and intercalated disc-mediated mechanotransduction

This study shows that DSG2 deficiency causes cardiac dysfunction by impairing Z-disc and intercalated disc mechanotransduction, leading to structural and functional cardiac defects.

Mavacamten facilitates myosin head ON-to-OFF transitions and shortens thin filament length in relaxed skeletal muscle

This study examines how mavacamten affects skeletal muscle structure by reducing ON-state myosin heads and shortening thin filament length, similar to its effects in cardiac muscle.

S2Tag, a novel affinity tag for the capture and immobilization of coiled-coil proteins: application to the study of human β-cardiac myosin

This paper identifies a novel epitope (S2Tag) recognized by an antibody that effectively tethers coiled-coil proteins, demonstrating its utility in studying β-cardiac myosin mechanics and disease mutations.

Missense variants in the myosin binding domains of MYBPC3 and MYBPHL impair sarcomere incorporation

The paper investigates how missense variants in MYBPC3 and MYBPHL affect sarcomere incorporation by expressing variants in cardiomyocytes and assessing their localization and stoichiometric effects.

MYBPHL nonsense mutations have poor sarcomere binding, are degraded, and cause abnormal contraction

The paper investigates MYBPHL nonsense mutations, showing they impair sarcomere incorporation, lead to protein degradation, and cause contractile defects in cardiomyocytes.

Genetic, Clinical, and Sociodemographic Profile in Individuals with Diagnosis or Family History of Hypertrophic Cardiomyopathy: Insights from a Prospective Cohort

This study examines genetic, clinical, and sociodemographic profiles of individuals with HCM or family history of SCD, finding higher genetic variant rates in HCM-diagnosed individuals and those with family history of SCD.

The G256E HCM mutation prolongs relaxation via altered nucleotide handling

This study investigates how the G256E HCM mutation affects myosin function by altering nucleotide handling, leading to prolonged relaxation and contributing to hypertrophic cardiomyopathy.

Early Subclinical and Sex-Specific Cardiac Remodeling Precedes HeartFailure in Zebrafish with Human Actin T126I Mutation.

This study shows that a human actin mutation causes sex-specific cardiac remodeling and dilated cardiomyopathy in zebrafish, with females showing more severe symptoms.

Danicamtiv reduces myosin's working stroke but enhances contraction by activating the thin filament

This study investigates danicamtiv's effects on cardiac myosin mechanics and shows it enhances contraction by altering crossbridge kinetics and thin filament activation.

Thin Filament Interaction and Ca2+-Desensitization Effect of the C-Terminal End Peptide of Cardiac Troponin T Where Loss of Function Mutations Cause Hypertrophic Cardiomyopathy

This study investigates the function of the C-terminal end peptide of cardiac troponin T and shows that HCM mutations impair its Ca2+-desensitization effect, suggesting it as a potential drug target for heart failure.

PGM1 deficiency disrupts sarcomere and mitochondrial function in a stem-cell cardiomyocyte model

This paper investigates the role of PGM1 in cardiomyocytes using patient-derived stem cells, finding disruptions in sarcomere and mitochondrial function, and suggesting potential therapeutic targets.

Implementing Precision Medicine for Dilated Cardiomyopathy: Insights from The DCM Consortium

This study identifies barriers and needs for genetic evaluation in dilated cardiomyopathy through a survey and discussion with cardiologists, highlighting the need for improved reimbursement, education, and infrastructure.

Annotating the X-ray diffraction pattern of vertebrate striated muscle

The paper uses an atomic model of the human cardiac thick filament to compute contributions of different components to X-ray diffraction patterns, confirming some interpretations and contradicting others.

Spatially resolving how phosphorylation affects β-cardiac myosin activity in porcine myofibril sarcomeres with single molecule resolution

This study uses single molecule imaging to analyze how phosphorylation affects myosin activity and cardiac reserve in porcine sarcomeres, identifying distinct kinetic states and their modulation by phosphorylation.

Synergistic Notch-WNT Activation Underlies Pediatric Dilated Cardiomyopathy

This study identifies synergistic Notch-WNT signaling activation in pediatric dilated cardiomyopathy and shows its inhibition improves cardiac function.

Desmoplakin Haploinsufficiency Underlies Cell-Cell Adhesion Failure in DSP Cardiomyopathy and is Rescued by Transcriptional Activation

This study shows that DSP haploinsufficiency causes cell-cell adhesion failure in cardiomyopathy and that increasing DSP expression rescues this defect.

CAMK2D causes heart failure in RBM20 cardiomyopathy

This study identifies CAMK2D overactivation as the cause of heart failure in RBM20 cardiomyopathy and shows pharmacological inhibition can reverse cardiac dysfunction.

Desmoplakin loss leads to PKC-dependent insertion of series sarcomeres and contractile dysfunction in cardiomyocytes

This study shows that desmoplakin loss causes PKC-dependent sarcomere shortening and contractile dysfunction in cardiomyocytes, leading to heart failure.

Myosin modulator Aficamten inhibits force in cardiac muscle by altering myosin's biochemical activity without changing thick filament structure

This paper shows Aficamten inhibits cardiac myosin ATPase without changing thick filament structure, unlike Mavacamten, leading to similar force reduction but different kinetic effects.

Clinical Validity of Autosomal Dominant ALPK3 Loss-of-function Variants as a Cause of Hypertrophic Cardiomyopathy

The paper evaluates the clinical validity of heterozygous ALPK3 loss-of-function variants as a cause of hypertrophic cardiomyopathy, finding strong gene-disease association with reduced penetrance.

Titin cleavage impairs cardiac mechanical connectivity to drive diastolic failure and fibrosis

This study shows that titin cleavage in mice causes concentric cardiac remodeling, diastolic dysfunction, and fibrosis by disrupting mechanical connectivity.

An ALPK3 truncation variant causing autosomal dominant hypertrophic cardiomyopathy is partially rescued by mavacamten

This study identifies an ALPK3 truncation variant causing HCM and shows that mavacamten partially rescues cardiac contractility and calcium handling defects in a mouse model.

Dynamics of β-cardiac myosin between the super-relaxed and disordered-relaxed states

This study investigates the dynamics between the super-relaxed (SRX) and disordered-relaxed (DRX) states of β-cardiac myosin, showing they are in rapid equilibrium and how mutations and inhibitors affect this balance.

Progression of the cardiac phenotype of the DE50-MD dog model of Duchenne Muscular Dystrophy, corroborating results of cardiac magnetic resonance imaging with pathology up to 36 months of age.

This study tracks cardiac changes in DE50-MD dogs with DMD, showing worsening fibrosis and function decline over time, validated by CMR and histopathology.

A myofilament lattice model of Drosophila flight muscle sarcomeres based on multiscale morphometric analysis during development

This study identifies factors affecting sarcomere size measurements, introduces a validated tool for precise analysis, and presents a model of Drosophila flight muscle sarcomere growth during development.

The preclinical cardiac phenotype of the DE50-MD dog model of Duchenne muscular dystrophy.

This study describes the cardiac phenotype of DE50-MD dogs, a dystrophin-deficient model of DMD, showing early cardiac changes similar to human DMD patients.

Evaluation of polygenic score for hypertrophic cardiomyopathy in the general population and across clinical settings

This study evaluates polygenic scores for hypertrophic cardiomyopathy (HCM) in the general population and clinical settings, showing increased risk with higher scores and potential for clinical application.

Investigating the effects of blebbistatin on actomyosin interactions in myofibrils and isolated myofilaments

This study investigates how blebbistatin affects force and velocity generation in actomyosin interactions across different scales, showing dose-dependent reductions in force and velocity.

Mavacamten inhibits myosin activity by stabilising the myosin interacting-heads motif and stalling motor force generation

This paper investigates how mavacamten inhibits myosin activity by stabilizing the interacting-heads motif and affecting cardiac muscle relaxation and contraction.

A fluorescent folding reporter uncovers myosin misfolding as a driver of Hypertrophic Cardiomyopathy

This study identifies myosin misfolding as a driver of HCM using a fluorescent reporter and C. elegans model, showing dietary restrictions can reverse defects via autophagy.