Myofilament dysfunction in diastolic heart failure

Figures

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  Fig. 1. a Hierarchical scheme of cardiac structures. Bundles of myofibrils group together to form heart tissue. A bundle of myofibrils wrapped by sarcolemma and composed of the repeats of sarcomeres. SR establishes a mesh-like structure to cover the myofibers. Invagination of the sarcolemma, known as the T-tubule, is located transversely to the sarcomere and forms close contact with the SR. Mitochondria located next to the myofibers along the t-tubules and SR. b Intracellular Ca2+ cycling in cardiomyocytes. After depolarizing the sarcolemma, a small quantity of Ca2+ enters the sarcoplasm via the DHPR of the T-tubule, activating a rapid and large influx of Ca2+ release from inside SR via the RyR2. NCX is the main mechanism by which Ca2+ is released from cells. Activation of the SERCA2 pump regulated by its binding partner PLN promotes the reuptake of cytosolic Ca2+ into the SR. Ca+2, calcium; DHPR, dihydropyridine receptor; K, potassium; Na/K, Na+/K+-pump membrane receptor; NCX, sodium–calcium exchanger; PLN, phospholamban; SERCA-2, sarco/endoplasmic reticulum Ca2+-ATPase; SR, sarcoplasmic reticulum

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  Fig. 2. Schematic illustration of the cardiac β-myosin heavy chain (β-MHC). β-MHC contains two heavy chains (tail), an essential light chain (ELC), a regulatory light chain (RLC), a myosin neck chain (S2), and a head domain (S1). The two light chains of myosin are located near the myosin head and facilitate calcium-dependent force transduction by the myosin head domain. In addition, myosin ATPase can cause hydrolysis ATP to provide energy for actomyosin contraction

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  Fig. 3. A schematic representation of contraction and relaxation with the interaction between troponin and other thin filament components. CaM, Calmodulin; cMyBP-C, cardiac myosin binding protein-C; CPI-17, C-kinase-potentiated protein phosphatase 1 inhibitor of 17 kDa; MLCK, myosin light-chain kinase; MLCP, myosin light-chain phosphatase; PKA, protein kinase A; TnI, troponin I; TnC, troponin C; TnT, troponin T; Tm, tropomyosin

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  Fig. 4. Subunit structure of cardiac heart myosin target phosphatase. KVKF motif, M20, 20 kDa small regulatory subunit; PP1cβ binding site; P, phosphorylation site; PPP1R12C, protein phosphatase 1 regulatory subunit 12C; PPPP1Cβ; protein phosphatase 1 catalytic subunit beta

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  Fig. 5. Characterization of diastolic dysfunction by echocardiography. BP, Blood pressure; EKG, electrocardiogram; TD, tissue Doppler; E, the velocity of blood flow across the mitral valve during early diastolic; A, velocity of blood flow across the mitral valve during atrial contraction; Aʹ, velocity of myocardial tissue relaxation during atrial contraction; Eʹ, the velocity of myocardial tissue relaxation during early diastole