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- W2069897707 abstract "Cardiac myosin binding protein C (cMyBP-C) is a sarcomeric protein that plays an essential role in the regulation of cardiac contraction. Until recently, cMyBP C was thought to hamper cross bridge cycling trough interaction of its N-terminus with the heads of myosin. However, the N-terminal domains of cMyBP-C can also bind with actin and this interaction could well explain the currently known functions of cMyBP-C. For instance, by forming a connection between the thin and the thick filament cMyBP-C could pose a load on the sarcomere and alter its visco-elastic properties. Additionally, cMyBP-C could alter the activation state of the thin filament by intervening with the position of tropomyosin. To study the physiological relevance of an interaction between cMyBP-C and actin, we created a transgenic mouse with a point mutation (L348P) that increases the binding affinity between cMyBP-C and actin in vitro. We hypothesized that stronger binding between cMyBP-C and actin will cause- through afore mentioned mechanisms, which have been demonstrated in different in vitro studies- stiffer cardiomyocytes which would ultimately lead to diastolic dysfunction in the hearts of L348P-Tg mice. Results show that the left atria of L348P-Tg mice are significantly enlarged. Echocardiograms in 12 week old animals demonstrated misshapen E and A waves, making diastolic function difficult to determine. Interestingly, pulse wave and tissue Doppler images were more defined in 24 weeks old mice. Preliminary data show decreased early blood flow over the mitral valve (E) and mitral valve movement (E’) in L348PTg mice, indicative of a stiffer left ventricle. In correspondence with that, isovolumetric relaxation time was prolonged. At neither age we observed systolic dysfunction. Additional in-depth hemodynamic studies to characterize the mechanisms of cardiac function longitudinally in L348P-Tg mice are ongoing." @default.
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- W2069897707 date "2015-01-01" @default.
- W2069897707 modified "2023-09-30" @default.
- W2069897707 title "The Physiological Relevance of Interactions between cMyBP-C and Actin Studied in a Transgenic Mouse Model" @default.
- W2069897707 doi "https://doi.org/10.1016/j.bpj.2014.11.737" @default.
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