Stretch your heart—but not too far: The role of titin mutations in dilated cardiomyopathy

Abstract

Cardiomyopathies are a heterogeneous group of diseases that negatively affect heart structure and function. An enlarged and weakened left ventricle (LV) characterizes dilated cardiomyopathy (DCM). Clinical studies have reported that approximately 50% of patients with DCM have a first-degree relative affected or likely to be affected, implicating a genetic cause. However, mutations have been found only in a small subgroup of patients. Titin, encoded by the TTN gene, is a sarcomeric protein present in skeletal muscle, smooth muscle, and cardiac muscle and is highly involved in the mechanotransduction and stretch of the heart muscle. The advantages and disadvantages of cardiac adaptation to stress and stretch have been the subject of several studies highlighting the role of titin in development and disease, summarized in recent review articles. With its discovery often dated back to 1976 when it was still called “connectin,”6 titin has been highlighted in cardiac physiology/medicine because of its possible contribution to the Frank–Starling mechanism and its implication in DCM