Cardiomyopathy and Myosin Studies

Cardiac myofibril networks induce shear stress

The paper uses a finite element model informed by myofibril orientations in sheep cardiomyocytes to show that myofibril networks generate unique shear stresses during contraction.

Abnormal ventricular wall patterning precedes and drives MYBPC3 hypertrophic cardiomyopathy

This study identifies abnormal ventricular wall patterning as a driver of MYBPC3-related hypertrophic cardiomyopathy through disrupted cardiomyocyte proliferation and Prdm16 regulation.

Molecular mechanics of smooth muscle contraction and relaxation modulated by caldesmon

This study measures the molecular effects of caldesmon on smooth muscle myosin force generation and relaxation using a laser-trap assay, showing CaD inhibits force and accelerates relaxation.

Circulating miRNA-Protein Signatures Predict Outcomes in Pediatric Dilated Cardiomyopathy

This study identifies circulating miRNA and protein signatures that predict clinical outcomes in pediatric dilated cardiomyopathy with high discriminatory accuracy.

Single-molecule analysis sheds light on cardiac myosin dysfunction due to hypertrophic cardiomyopathy mutation A57D in ventricular myosin light chain-1 (MLC1v)

This study investigates the molecular mechanism of cardiac myosin dysfunction caused by the A57D mutation in MLC1v using single-molecule analysis and computational modeling.

Myosin binding protein-C limits strain induced cross-bridge detachment in response to rapid stretch in cardiac and skeletal muscle

This study shows that different MyBP-C paralogs have similar effects on cross-bridge cycling but distinct responses to rapid stretch, with MyBP-C limiting strain-induced detachment in fast-twitch muscles.

Phase-targeting rapid cryofixation of the beating heart and histological analysis unveil contractile state-dependent sarcomere dynamics

The paper uses phase-targeting cryofixation to analyze sarcomere length dynamics in rat hearts, revealing contractile state-dependent spatial heterogeneity.

Phosphoproteomics of Hypertrophic Cardiomyopathy Patient Myocardium and Novel hiPSC-CM Model Reveal Protein Kinase A as a Modulator of Microtubule Repolymerization

The paper identifies altered microtubule post-translational modifications in hypertrophic cardiomyopathy and shows protein kinase A modulates microtubule repolymerization in patient-derived hiPSC-CMs.

Myosin Filaments of Vertebrate Skeletal and Cardiac Muscle are Highly Similar, but not Identical

The paper compares myosin filament structures across vertebrate skeletal and cardiac muscle, finding high similarity but differences in myosin binding protein C positioning.

Cryo-ET reveals nanoscale thick filamentdisorganization in MYH7 P710R hypertrophiccardiomyopathy cardiomyocytes

This study uses cryo-ET to show that MYH7 P710R mutations disrupt thick filament organization in HCM cardiomyocytes, leading to sarcomeric disarray and ribosome infiltration.

Spatial control of myosin regulatory light chain phosphorylation modulates cardiac thick filament mechano-sensing

This study shows that phosphorylation of cardiac myosin regulatory light chain (RLC) is spatially controlled and modulates mechano-sensing in cardiac thick filaments.

Ulacamten: A Novel, RLC-Targeting Cardiac Myosin Inhibitor for Potential Treatment of Cardiac Hypercontractility, Including HFpEF

This paper describes ulacamten, a novel cardiac myosin inhibitor with distinct binding and inhibitory properties compared to existing CMIs, showing efficacy in improving cardiac function in a rodent model of HFpEF.

Cardiomyopathy-Associated and Basic Residue Mutations in Myopalladin Alter Actin Binding, Bundling, and Structural Stability

This paper identifies conserved basic residue clusters in the Ig3 domain of myopalladin (MYPN) critical for actin binding and bundling, showing that cardiomyopathy-associated mutations disrupt these interactions and lead to abnormal subcellular localization.

Utility of polygenic risk scores in diagnostic genetic testing for dilated cardiomyopathy

This study evaluates polygenic risk scores (PRS) in dilated cardiomyopathy (DCM) patients, finding higher PRS in those without monogenic variants and TTN-related DCM, suggesting polygenic contributions.

Kinetic Modeling of mant-ATP Turnover to Interpret the Biochemically Defined Myosin SRX State

This paper develops a kinetic model to interpret mant-ATP fluorescence decay in myosin SRX state measurements, showing that decay phases result from label redistribution, not equilibrium states.

Location-Dependent Differences in Cardiac and Skeletal Muscle Dysfunction Associated With Truncating Titin (ttn.2) Variants

This study investigates how truncating variants in the ttn.2 gene affect cardiac and skeletal muscle function in zebrafish, showing location-specific differences in disease severity and phenotypes.

The Epigenetic Regulator Histone Demethylase KDM5A is Activated and Pathogenic in a Mouse Model of Heart Failure

This study shows that KDM5A is activated in heart failure and its deletion improves cardiac function and gene expression in a mouse model.

Pathogenetic mechanisms of muscle-specific ribosomes in dilated cardiomyopathy

The paper identifies a pathogenetic mechanism for RPL3L-linked dilated cardiomyopathy, showing that gain-of-toxicity variants in muscle-specific ribosomes cause severe neonatal heart failure.

Impact of Cardiomyopathy and Arrhythmia Genetic Testing on Clinical Management Decisions

This study examines how genetic testing results for cardiomyopathy and arrhythmia influence clinical management decisions, finding that positive results lead to more management changes.

A myosin hypertrophic cardiomyopathy mutation disrupts the super-relaxed state and boosts contractility by enhanced actin attachment

This paper investigates the HCM mutation M493I in β-cardiac myosin, showing it disrupts the super-relaxed state, slows ADP release, and enhances actin attachment and force production, leading to hypercontractility.

Multiparametric Assessment of TNNI3 Variant Phenotypes in Human iPSC-Cardiomyocytes Correlates with Disease Severity in Patients

This study assesses TNNI3 variant effects on hiPSC-CM physiology and links these findings to disease severity in cardiomyopathy patients.

Whole exome sequencing reveals UNC45B as a novel candidate gene functionally associated with Dilated Cardiomyopathy

The paper identifies UNC45B variants in DCM patients and shows they cause structural and functional defects leading to cardiac dysfunction.

Sub-sarcomeric regulation of thin and thick filaments in skeletal muscle myofibrils

The paper uses fluorescence polarization microscopy to study zone-specific regulation of myosin and actin activation in skeletal muscle sarcomeres, revealing distinct control mechanisms in different filament regions.

A non-muscle α-actinin is an intrinsic component of the cardiac Z-disc and regulates sarcomere turnover, contractility, and heart remodeling

This study identifies ACTN4 as a non-muscle α-actinin in cardiac sarcomeres, showing it regulates contractility, hypertrophy, and heart remodeling without disease hallmarks.

Comprehensive Genetic Study of Russian Hypertrophic Cardiomyopathy Identifies MYBPC3 c.3697C>T as the Predominant Variant in Pediatric and Adult Cohorts

This study identifies MYBPC3 c.3697C>T as a prevalent variant in Russian HCM patients, associated with distinct pediatric and adult phenotypes.

Molecular mechanisms of altered contraction with the β-myosin R403Q mutation in porcine ventricular muscle and a human stem cell-derived cardiomyocyte model.

This study investigates the R403Q mutation in beta-myosin heavy chain using porcine and human stem cell models, revealing altered contractile properties and mechanisms of hypercontractility and impaired relaxation.

Direct measurement of mavacamten and deoxyATP perturbation of the SRX/DRX ratio in porcine cardiac myofibrils using a simple, accessible and multiplexed approach

The paper measures how mavacamten and deoxyATP affect the SRX/DRX ratio in porcine cardiac myofibrils using a fluorescence imaging approach.

Identification and functional characterization of LDB3 gene variants in DCM patients from Indian Population

This study identifies and functionally characterizes LDB3 gene variants in Indian DCM patients, finding six novel missense variants that affect protein structure, expression, and Z-disc integrity.

ZEB1 Is a Key Regulator of Cardiomyocyte Structure and Function

This study investigates ZEB1's role in cardiomyocyte structure and function, finding that its deletion causes sarcomere damage, mitochondrial dysfunction, and dedifferentiation, particularly in females.

Spatial genomics of the cardiac sarcomere

The paper integrates genomic and structural data to identify variant intolerance regions in cardiac sarcomere genes and links them to disease mechanisms in hypertrophic cardiomyopathy.