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- W2024793063 abstract "Missense mutations in the TNNC1 gene encoding cardiac and slow skeletal troponin C (c/ssTnC) are associated with phenotypic outcomes of hypertrophic cardiomyopathy (HCM). The impact of HCM c/ssTnC mutations in skeletal muscle structure and function is unknown; therefore, we examined the effect of an HCM-associated c/ssTnC A8V mutation on myosin heavy chain (MHC) isoform expression, contractile properties of different skeletal muscles, and cardiac autonomic function in a homozygous knock-in mouse (KI-TnC-A8V+/+). The distribution of MHC I/II isoforms in various muscles from 3-month old male WT and KI-TnC-A8V+/+ mice were analyzed by glycerol SDS-PAGE and the muscle/body weight ratios (M/BW) were recorded. Mechanics of contraction in isolated intact soleus muscle, running/endurance capacity and heart rate variability (HRV) were also measured. In comparison to the WT mice, MHC isoform switching was observed in diaphragm (increased MHCIIb, decreased MHCI) and soleus (decreased MHCIIa, increased MHCI) muscles of KI-TnC-A8V+/+ mice; while, the M/BW ratio was unchanged for all tested muscles. The force vs frequency relationship at 15Hz and the t1/2 of relaxation increased in the intact soleus muscle of KI-TnC A8V+/+ mice in comparison to the WT; whereas, no changes in maximal force, time-to-twitch peak, velocity and power output were observed. In endurance and HRV tests, KI-TnC-A8V+/+ mice had a lower running distance capacity and their global autonomic, cardiovagal, and baroreflex activities were significantly reduced compared to WT. In spite of the increase in type I fibers in soleus muscle of mice expressing c/ssTnC A8V, they display reduced endurance capacity. These findings suggest that the slow skeletal muscle is trying to compensate for the cardiac dysfunction caused by the c/ssTnC A8V+/+ mutation. Supported by NIH HL103840 (JRP)." @default.
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- W2024793063 date "2015-01-01" @default.
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- W2024793063 title "Structural and Functional Changes in Skeletal Muscles in an A8V-Troponin C Hypertrophic Cardiomyopathy Knock-In Mouse Model" @default.
- W2024793063 doi "https://doi.org/10.1016/j.bpj.2014.11.3233" @default.
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