Titin cleavage alters the myocardial elastic network and remodels the heart

Abstract

Proteolytic cleavage of the giant elastic protein titin causes the heart to lose elastic recoil, leading to a restrictive phenotype, impaired ventricular filling, disrupted cell–matrix connectivity, and immediate fibroblast activation followed by fibrosis. These findings identify titin-based restoring forces as essential regulators of cardiac mechanical homeostasis.