The Importance of N2BA Titin in Maintaining Cardiac Homeostasis and Its role in Dilated Cardiomyopathy

Titin is the third myofilament type of the cardiac sarcomere and performs important functions that include generating passive tension. Changes in titin expression are associated with cardiac dysfunction and titin is one of the main genes linked to dilated cardiomyopathy (DCM). DCM is frequently associated with changes in expression of N2BA titin, one of the two major titin isoforms found in the heart (the other isoform being the N2B isoform). Whether altered expression of N2BA titin causes DCM or is a secondary change remains unclear. Studying a mouse model, which specifically shortens the PEVK region of the N2BA isoform (Ttndelta112-158), showed reduced expression of the N2BA isoform of titin and the titin-binding protein MARP1, leading to a progressively dilated cardiac phenotype.