Role of Titin Phosphorylation in Myocardial Stiffness Changes during Cardiomyopathies

The review provides a brief analysis of the current knowledgeof such a post-translational modification of titin as phosphorylation,with a focus on changes that occur during the development of heartdiseases. Studies using animal models of heart diseases and cardiacbiopsy from patients with various pathologies reveal changes inthe level of titin phosphorylation compared to healthy controls.The development of cardiac pathology is typically accompanied byhyperphosphorylation of the S11878 site and hypophosphorylationof the S12022 site in the titin PEVK region, as well as changesin the level of site phosphorylation in the titin N2B region. Thecooperative functional effect of these changes is an increase inthe stiffness of cardiomyocytes and cardiac muscle as a whole, basedon the viscoelastic properties of titin. Changes in the latter,in turn, result from hypo- or hyperphosphorylation of certain titinsites. The review also addresses a number of therapeutic approachesaimed at modifying titin phosphorylation levels as a means to manageviscoelastic properties of the pathological myocardium in orderto normalize its contractility.