Dilated cardiomyopathy-mediated heart failure induces a unique skeletal muscle myopathy with inflammation

摘要: Skeletal muscle myopathy and exercise intolerance are diagnostic hallmarks of heart failure (HF). However, the molecular adaptations skeletal muscles during dilated cardiomyopathy (DCM)-mediated HF not completely understood. structure function were compared in wild-type (WT) cardiac myosin binding protein-C null mice (t/t), which develop DCM-induced HF. Cardiac was examined by echocardiography. Exercise tolerance measured using a graded maximum treadmill running test. Hindlimb assessed vivo from measurements plantar flexor strength. Inflammatory status evaluated expression inflammatory markers presence specific immune cell types gastrocnemius muscles. Muscle regenerative capacityat days 3, 7, 14 after eccentric contraction-induced injury determined number phenotypically new adult fibers gastrocnemius, functional recovery flexion torque. t/t developed association with profound intolerance, consistent previous reports. Compared to WT, mouse hearts show significant hypertrophy atria ventricles reduced fractional shortening, both systolic diastolic. In parallel, exhibit weakness myopathy. produce less peak isometric torque (Po), more slowly (+ dF/dt), relax (− dF/dt, longer half-relaxation times,1/2RT). Gastrocnemius have greater smaller diameters central nuclei. Oxidative fibers, type I IIa, significantly cross-sectional areas These fiber phenotypes suggest ongoing repair regeneration under homeostatic conditions. addition, ability recover regenerate acute is impaired mice. Our studies concluded that induces unique characterized decreased strength, atrophy oxidative types, inflammation damage homeostasis, injury. Furthermore, this likely contributes exacerbates intolerance. Therefore, efforts therapeutic interventions treat should be considered.