Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Monday Speaker Abstracts

MODULATORS OF CARDIAC MUSCLE RELAXATION, AND THEIR ROLE IN CARDIAC PATHOLOGY Jolanda van der Velden ; 1 Amsterdam UMC, Physiology, Amsterdam, The Netherlands Less than 20 years ago, awareness increased that impaired muscle relaxation underlies different forms of cardiac disease. For a long time, reduced contractility was believed to be the major defect in heart failure, and therapies aimed to enhance force generation of cardiomyocytes. While fibrosis was and still is considered tob e a key player of stiffening of the heart muscle, in recent years it has become evident that several proteins underlie passive tension generation. Studies in cardiac biopsies from patients with heart failure and preserved ejection fraction, previously known as diastolic heart failure, revealed increased passive tension generated by isolated membrane-permeabilized cardiomyocytes. The high passive tension could be normalized to values found control cardiomyocytes by exogenous protein kinase A and protein kinase G. Studies indicate that a deficit in titin phosphorylation underlies increased cardiomyocyte passive tension. In heart failure, complex changes in extracellular remodeling, and titin phosphorylation and isoform composition underlie impaired relaxation of the heart. In addition to myofilament protein changes, cytoskeletal remodeling, and in particular microtubule detyrosination, has been observed in hypertrophic and dilated forms of human cardiac disease. Changes in extracellular, myofilament and cytoskeletal remodeling depend on the initial cause and severity of cardiac disease. During the presentation, an overview will be given of reported changes in human heart disease.

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