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Mechanical Stretching Simulates Cardiac Physiology and Pathology through Mechanosensor Piezo1

The dynamics of a living body enables organs to experience mechanical stimulation at cellular level. The human cardiomyocytes cell line provides a source for simulating heart dynamics; however, a limited understanding of the mechanical stimulation effect on them has restricted potential applications...

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Detalles Bibliográficos
Autores principales: Wong, Tzyy-Yue, Juang, Wang-Chuan, Tsai, Chia-Ti, Tseng, Ching-Jiunn, Lee, Wen-Hsien, Chang, Sheng-Nan, Cheng, Pei-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262272/
https://www.ncbi.nlm.nih.gov/pubmed/30400259
http://dx.doi.org/10.3390/jcm7110410
Descripción
Sumario:The dynamics of a living body enables organs to experience mechanical stimulation at cellular level. The human cardiomyocytes cell line provides a source for simulating heart dynamics; however, a limited understanding of the mechanical stimulation effect on them has restricted potential applications. Here, we investigated the effect of mechanical stimulation on the cardiac function-associated protein expressions in human cardiomyocytes. Human cardiomyocyte cell line AC16 was subjected to different stresses: 5% mild and 25% aggressive, at 1 Hz for 24 h. The stretched cardiomyocytes showed down-regulated Piezo1, phosphorylated-Ak transforming serine473 (P-AKT(S473)), and phosphorylated-glycogen synthase kinase-3 beta serine9 P-GSK3β(S9) compared to no stretch. In addition, the stretched cardiomyocytes showed increased low-density lipoprotein receptor-related protein 6 (LRP6), and phosphorylated-c-Jun N-terminal kinase threonine183/tyrosine185 (P-JNK(T183/Y185)). When Piezo inhibitor was added to the cells, the LRP6, and P-JNK(T183/Y185) were further increased under 25%, but not 5%, suggesting that higher mechanical stress further activated the wingless integrated-(Wnt)-related signaling pathway when Piezo1 was inhibited. Supporting this idea, when Piezo1 was inhibited, the expression of phosphorylated-endothelial nitric oxide synthase serine1177 (P-eNOS(S1177)) and release of calcium ions were reduced under 25% compared to 5%. These studies demonstrate that cyclic mechanical stimulation affects cardiac function-associated protein expressions, and Piezo1 plays a role in the protein regulation.