Role of Titin Phosphorylation in Myocardial Stiffness Changes during Cardiomyopathies

Abstract

The review provides a brief analysis of the current knowledge of such a post-translational modification of titin as phosphorylation, with a focus on changes that occur during the development of heart diseases. Studies using animal models of heart diseases and cardiac biopsy from patients with various pathologies reveal changes in the level of titin phosphorylation compared to healthy controls. The development of cardiac pathology is typically accompanied by hyperphosphorylation of the S11878 site and hypophosphorylation of the S12022 site in the titin PEVK region, as well as changes in the level of site phosphorylation in the titin N2B region. The cooperative functional effect of these changes is an increase in the stiffness of cardiomyocytes and cardiac muscle as a whole, based on the viscoelastic properties of titin. Changes in the latter, in turn, result from hypo- or hyperphosphorylation of certain titin sites. The review also addresses a number of therapeutic approaches aimed at modifying titin phosphorylation levels as a means to manage viscoelastic properties of the pathological myocardium in order to normalize its contractility.