TMAO aggravates heart failure by promoting T-tubule remodeling in adult mouse cardiomyocytes |
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Authors: | JIN Bu JI Fang-fang ZUO An-jun LIU Hui-ting QI Lin HE Yun WANG Qing-yao ZHAO Peng |
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Institution: | 1.Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China;2.School of Basic Medicine, Medical College, Qingdao University, Qingdao 266071, China;3.Qingdao Sanatorium of Shandong Province, Qingdao 266071, China;4.Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, Chinacom |
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Abstract: | AIM To investigate the role of trimethylamine N-oxide (TMAO) in T-tubule in cultured adult mouse cardiomyocytes. METHODS T-tubule imaging was used to detect T-tubule network in cardiomyocytes. Ca2+ handling dysfunction was identified by confocal Ca2+ imaging. Tubulin densification and polymerization in the cardiomyocytes were assessed by Western blot and immunofluorescence staining. Echocardiography was used to detect cardiac function in the mice fed on TMAO and chow diet. RESULTS Compared with control group, the T-tubule density and T-tubule power of the mouse cardiomyocytes cultured with TMAO were significantly decreased (P<0.01). Compared with control group, the mean amplitude of Ca2+ transients in TMAO group was decreased (P<0.01), while the time to reach the Ca2+ transient peak and the dyssynchrony index increased (P<0.01). Compared with control group, the power of junctophilin-2 (JPH2) in the mouse cardiomyocytes treated with TMAO was decreased (P<0.01). Significant JPH2 accumulation was observed at the edge of the cardiomyocytes (P<0.01). Compared with control group, the microtubule density in TMAO group was significantly higher (P<0.01), and microtubule aggregation was enhanced (P<0.01). Compared with the mice in control group fed on a normal diet, the TMAO-fed mice had significantly lower systolic function and left ventricular ejection fraction (P<0.05). CONCLUSION TMAO impairs cardiac function via the promotion of tubulin polymerization, subsequent JPH2 translocation and T-tubule remodeling, which provides a novel mechanism for the relationship between heart failure and elevated TMAO. |
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Keywords: | Trimethylamine N-oxide Heart failure T-tubule Tubulin Junctophilin-2 |
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