Cardiomyopathy and Myosin Studies

This study uses iPSC-derived heart tissue models to show that mechanical stress exacerbates HCM-linked MYBPC3 mutations, leading to structural and functional cardiac pathology.

This paper develops a computational model of HCM cardiomyocyte signaling and metabolism to predict genotype-to-phenotype mechanisms and identify potential drug targets.

This study shows that a myosin ATPase inhibitor reverses HCM phenotypes in pediatric iPSC-cardiomyocytes, with effects dependent on the underlying genetic variant.

This paper examines how the E525K mutation in human β-cardiac myosin affects its super-relaxed state and contractility in dilated cardiomyopathy.

This study shows that MyBP-CC1C7 domains form C-links and stabilize myosin OFF states, affecting crossbridge kinetics and sarcomere function.

The paper investigates how titin-based forces affect cardiac myofilament structures under stretch, supporting the Frank-Starling mechanism.

This study compares the effects of homologous mutations in three muscle myosin isoforms, finding divergent molecular impacts that correlate with disease severity.

The paper develops a multiscale model of muscle contraction that explains force depression by integrating molecular and cellular measurements from rabbit psoas muscle.

This study decouples structural OFF/ON states from biochemical SRX/DRX states in myosin using X-ray diffraction and ATP assays in porcine myocardium.

The paper identifies amino acid substitutions in titin domains that increase hydrophilicity and cause dilated cardiomyopathy by destabilizing the protein structure.

This study reveals the 3D structure of relaxed cardiac sarcomeres using cryo-electron tomography, showing how thick filament components interact and function in muscle contraction.

This paper solves the cryo-EM structure of the human cardiac myosin filament, revealing the arrangement of myosin, cMyBP-C, and titin and their functional interactions.

This study investigates how mutations in MYH7 and MYH2 genes affect myosin structure and function, finding that they disrupt coiled-coil structure and increase ATP consumption without affecting contractile function.

This paper estimates the penetrance of rare variants in cardiomyopathy genes using cross-sectional data from genetic testing, finding substantial penetrance for dominant cardiomyopathies and variant-specific differences.

This study establishes a canine model for echocardiography-guided percutaneous intramyocardial septal cryoablation and shows its safety and feasibility in reducing interventricular septum.

The paper uses top-down proteomics to analyze MLC-1 and -2 isoform expression in human heart chambers, revealing chamber-specific patterns and a novel PTM.

This study identifies genetic differences between pediatric and adult cardiomyopathy, finding more constrained variants in childhood cases and female patients.

The paper evaluates alternative models for Pi-release timing relative to the power-stroke in actomyosin energy transduction and proposes critical tests for a unified understanding.

The paper identifies heterozygous missense variants in ACTC1 as the cause of distal arthrogryposis with congenital heart defects in five families.

This study investigates how cardiomyopathy-associated variants in the α-actinin-2 actin-binding domain affect its structure and function, finding that some variants disrupt actin binding and may contribute to disease.

This study identifies perturbations in arachidonic acid metabolism across primary cardiomyopathies using RNA-seq data and gene set analysis.

This study shows that ablating PALLD in adult hearts causes dilated cardiomyopathy with intercalated disc abnormalities and fibrosis, suggesting PALLD's essential role in cardiac function.

This paper shows that mavacamten stabilizes myosin in off states, which can still be recruited by physiological inotropic effectors to maintain cardiac function.

The paper develops a signaling network model to investigate genotype-to-phenotype mechanisms in familial cardiomyopathy, showing it can predict experimental outcomes and suggest therapeutic strategies.

The paper uses nanobodies and DNA-PAINT to show that Drosophila titin homologs Sallimus and Projectin are staggered in flight muscle sarcomeres.

This paper evaluates a communication aid for returning genetic results in HCM families, finding no significant difference in communication effectiveness but noting higher knowledge scores in the intervention group.

The paper identifies FLNC loss-of-function variants in a clinical population and finds they are associated with increased odds of arrhythmogenic cardiomyopathy phenotypes.

This study uses whole-genome sequencing to identify regulatory and novel genic variants contributing to childhood cardiomyopathy.

The paper investigates how mono- and bi-allelic ACTN2 mutations cause cardiomyopathy through distinct mechanisms using patient-derived iPSC-cardiomyocytes and CRISPR-Cas9 editing.