Cardiac sarcomere proteins

Cardiac sarcomere proteins are the fundamental components of the contractile apparatus in heart muscle cells, organized into thick and thin filaments. The primary proteins include cardiac myosin (MYH7), actin, tropomyosin, the troponin complex (TnI, TnT, TnC), and cardiac myosin-binding protein C (MYBPC3) [1, 2]. These proteins interact in a calcium-dependent manner to facilitate the cross-bridge cycle, which generates the mechanical force necessary for cardiac systole and allows for relaxation during diastole [3]. Mutations in the genes encoding these proteins are the most common cause of inherited cardiomyopathies, leading to either hypercontractility (as seen in hypertrophic cardiomyopathy) or hypocontractility (as seen in dilated cardiomyopathy) [4]. Therapeutic targeting of these proteins has emerged as a precision medicine approach to modulate cardiac contractility directly at the molecular level [5]. For example, cardiac myosin inhibitors like mavacamten and aficamten are used to treat obstructive hypertrophic cardiomyopathy by reducing the number of myosin heads available for power strokes [6, 7]. Conversely, cardiac myosin activators like omecamtiv mecarbil are designed to increase the duration of the force-generating state to treat heart failure with reduced ejection fraction [8]. Additionally, calcium sensitizers like levosimendan target troponin C to enhance contractility without increasing intracellular calcium levels [9].

Other names

Cardiac myofilamentContractile apparatusSarcomeric proteinsCardiac contractile proteins

Direct modulation of the cardiac sarcomere through myosin inhibition (reducing cross-bridge formation), myosin activation (increasing the duration of the force-generating state), or calcium sensitization of troponin C.