Atrial light chain 1 (ALC-1) is expressed in embryonic and hypertrophied human ventricles but not in normal adult human ventricles. We investigated the effects of recombinant human atrial light chains (hALC-1) on the structure and enzymatic activity of synthetic filaments of ventricular myosin. The endogenous ventricular myosin light chain 1 (VLC-1) was partially replaced by recombinant hALC-1 yielding hALC-1 levels of 12%, 24% and 42%. This reconstitution of ventricular myosin with hALC-1 did not change the length of synthetic myosin filaments but led to more rounded myosin heads in comparison with those of control filaments. Actin-activated ATPase activity of myosin, a parameter of functional activity of molecular motor, amounted to 79.5 nmol P(i)/mg per min in control myosin filaments. Reconstitution with hALC-1 caused a profound increase of the actin-activated myosin ATPase activity in a dose dependent manner, for example, synthetic myosin filaments formed with 12%, 24% and 42% hALC-1 reconstituted myosin revealed the actin-activated ATPase activity increased by 18%, 26% and 36%, respectively, as compared to control. These results strongly suggest that in vivo expression of ALC-1 enhances ventricular myosin function, thereby contributing to cardiac compensation.
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Cardiol Rev
October 2024
Department of Cardiology, Royal Devon University Healthcare National Health Service Foundation Trust, Exeter, United Kingdom.
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by structural and functional abnormalities. Current management strategies, such as medications and septal reduction therapies, have significant limitations and risks. Recently, cardiac myosin inhibitors (CMIs) like mavacamten and aficamten have shown promise as noninvasive treatment options.
View Article and Find Full Text PDFAm J Cardiol
December 2024
Northwestern University, Feinberg School of Medicine, Chicago IL 60611; The Hypertrophic Cardiomyopathy Program at the Bluhm Cardiovascular Institute, Chicago IL 60611; Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Chicago IL 60611.
Background: Obstructive hypertrophic cardiomyopathy (HCM) is associated with significant morbidity due to left ventricular outflow tract (LVOT) obstruction. While alcohol septal ablation (ASA) is an established interventional treatment, mavacamten, a novel cardiac myosin inhibitor, has emerged as a non-invasive pharmacological alternative. Understanding the comparative efficacy of these two treatments is important for optimizing patient care.
View Article and Find Full Text PDFS-glutathionylation (SSG) is increasingly recognized as a critical signaling mechanism in the heart, yet SSG modifications in cardiac sarcomeric proteins remain understudied. Here we identified SSG of the ventricular isoform of myosin light chain 1 (MLC-1v) in human, swine, and mouse cardiac tissues using top-down mass spectrometry (MS)-based proteomics. Our results enabled the accurate identification, quantification, and site-specific localization of SSG in MLC-1v across different species.
View Article and Find Full Text PDFJACC Case Rep
November 2024
SingHealth Duke-NUS Genomic Medicine Centre, Duke NUS Medical School, Singapore.
Hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) are phenotypically distinct inherited cardiac diseases. This case report presents a woman aged 51 years with coinheritance of pathogenic/likely pathogenic variants of the β-myosin heavy chain ( p.Glu924Lys) and plakophilin 2 ( p.
View Article and Find Full Text PDFHeart Fail Rev
December 2024
Division of Cardiovascular Medicine, University of Virginia, 1215 Lee St Box 800158, Charlottesville, VA, 22908, USA.
Hypertrophic cardiomyopathy (HCM) is an inherited condition characterized by left ventricular, non-dilated hypertrophy in the absence of another secondary underlying cause. There has been an ongoing increase in the diagnosis of HCM over the past couple of decades, prompting further work in the area of pharmacological and interventional therapies. This scoping review aimed to summarize the traditional therapeutic options for HCM and to explore emerging research on novel cardiac myosin inhibitors (CMIs) as a new option for pharmacologic management of HCM.
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