Structure of the striated muscle, i.e., cardiac and skeletal muscles, represents

thick and thin filaments. The main components of the thick and thin filaments are myosin and actin, respectively, and the thin filaments are inserted into, and tethered by, the Z-band in a square array with the sarcomeric filaments from Inhibitors,research,lifescience,medical the neighboring sarcomere (2). Because the force generated by contraction of sarcomere can be transmitted through a complex network of proteins in the Z-band, the Z-band plays various important roles in the cardiomyocytes, i.e., sarcomeric organization and force transduction in cardiac muscle (3). The Z-band also mediates functional link between sarcolemma and nuclear membrane (4). Because the

Z-band is important in establishing the Inhibitors,research,lifescience,medical mechanical coupling of the sarcomere, functional defects in the sarcomere or Z-band proteins might lead to cardiac Inhibitors,research,lifescience,medical dysfunction. Indeed, abnormalities in the cytoarchitectural proteins including sarcomere/Z-band components have been identified in ICM (5). This review will focus on the role of saromere and cytoskeletal Z-band proteins in the pathogenesis of ICM. Hypertrophic cardiomyopathy (HCM) HCM is the most prevalent hereditary cardiac Pexidartinib nmr disease (1:500 Inhibitors,research,lifescience,medical of the general population for the disease phenotype) and one of the major causes of sudden cardiac death in the young, characterized by left ventricular (LV) hypertrophy, usually with the presence of a small LV cavity, accompanied by Inhibitors,research,lifescience,medical myofibrillar disarrays and diastolic dysfunction (6, 7). From the first full description of HCM, in 1958, as “asymmetrical hypertrophy of the heart in young adults” including

a sib-case with sudden cardiac death (8), it has been suggested that this disease is inheritable. Indeed, 50-70% of HCM patients have apparent family histories of the disease, which is consistent with autosomal dominant inheritance, almost suggesting that genetic abnormalities cause HCM (6). The etiology of HCM, however, had been unknown until 1990 when a mutation in MYH7 encoding cardiac β-myosin heavy chain was, for the first time, identified in a multiple family with HCM. After the discovery of MYH7 mutation as the HCM gene, hundreds of mutations in more than 20 genes were reported in HCM and HCM-like diseases (Table ​(Table1).1).