Titin: An endosarcomeric protein that modulates myocardial stiffness in DCM

Titin is the third myofilament of the cardiac muscle sarcomere, with a single molecule spanning the half sarcomere. Titin contains a molecular spring segment that generates passive force in sarcomeres stretched above the slack length and restoring forces in sarcomeres shortened below this length. The roles of titin in heart disease remain to be established. In this work we review recent developments in the understanding of titin's role in cardiac muscle. We focus on both short-term and long-term modulation of titin-based muscle stiffness, as well as on the recently discovered interplay between titin and actomysoin interaction, suggesting a possible role for titin in the Frank-Starling mechanism of the heart. Finally, we present evidence that suggests that titin plays a role in elevating passive stiffness of myocardium of dilated cardiomyopathy (DCM) hearts, via alterations in titin isoform expression.