Since cardiac relaxation is commonly impaired in heart failure caused by many different etiologies, identifying druggable targets is a common goal. While many factors contribute to cardiac relaxation, this review focuses on sarcomeric relaxation and dysfunction. Any alteration in how sarcomeric proteins interact can lead to significant shifts in sarcomeric relaxation that may contribute to diastolic dysfunction. Considering examples of sarcomeric dysfunction that have been reported in 3 different pathologies, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and heart failure with preserved ejection fraction, will provide insights into the role sarcomeric dysfunction plays in impaired cardiac relaxation. This will ultimately improve our understanding of sarcomeric physiology and uncover new therapeutic targets.
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http://dx.doi.org/10.1016/j.cophys.2022.100535 | DOI Listing |
bioRxiv
December 2024
Institute of Physiology II, University of Muenster; Muenster, Germany.
The first-in-its-class cardiac drug mavacamten reduces the proportion of so-called ON-state myosin heads in relaxed sarcomeres, altering contraction performance. However, mavacamten is not completely specific to cardiac myosin and can also affect skeletal muscle myosin, an important consideration since mavacamten is administered orally and so will also be present in skeletal tissue. Here, we studied the effect of mavacamten on skeletal muscle structure using small-angle X-ray diffraction.
View Article and Find Full Text PDFJ Physiol
December 2024
Department of Anatomy & Physiology, University of Melbourne, Melbourne, Australia.
Cardiometabolic syndromes including diabetes and obesity are associated with occurrence of heart failure with diastolic dysfunction. There are no specific treatments for diastolic dysfunction, and therapies to manage symptoms have limited efficacy. Understanding of the cardiomyocyte origins of diastolic dysfunction is an important priority to identify new therapeutics.
View Article and Find Full Text PDFJ Physiol
October 2024
The Leon Charney Division of Cardiology, New York University Grossmann School of Medicine, New York, NY, USA.
Atrial arrhythmias occur in 20-40% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and are associated with an increased risk of sustained ventricular arrhythmias and inappropriate implantable cardioverter-defibrillator shocks. The pathophysiology of atrial arrhythmias in ARVC remains unclear. Most cases of gene-positive ARVC are linked to pathogenic variants in the desmosomal gene plakophilin-2 (PKP2).
View Article and Find Full Text PDFBioact Mater
January 2025
Department of Chemical Engineering, Auburn University, Auburn, AL, United States.
PLoS One
October 2024
Department of Clinical Science and Services, Royal Veterinary College, Hatfield, London, United Kingdom.
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