An abnormal TRPV4-related cytosolic Ca2+ rise in response to uniaxial stretch in induced pluripotent stem cells-derived cardiomyocytes from dilated cardiomyopathy patients.
Biochim Biophys Acta Mol Basis Dis
; 1863(11): 2964-2972, 2017 11.
Article
em En
| MEDLINE
| ID: mdl-28754452
ABSTRACT
Dilated cardiomyopathy (DCM) is cardiac disease characterized by increased left ventricular chamber volume and decreased systolic function. DCM patient-specific human induced-pluripotent stem cells-derived cardiomyocytes (DCM-hiPSC-CMs) were generated. We found that uniaxial stretch elicited a cytosolic [Ca2+]i rise in hiPSC-CMs. Compared to control-hiPSC-CMs, DCM-hiPSC-CMs displayed a greater magnitude of [Ca2+]i responses to the cell stretch of 10-15% elongation in length. This stretch-induced [Ca2+]i rise was abolished by removal of extracellular Ca2+ and markedly attenuated by TRPV4 inhibitors HC-067047 and RN-1734. Application of nifedipine and tranilast also reduced the [Ca2+]i response but to a lesser degree. Moreover, the augmented [Ca2+]i was decreased by cytochalasin D treatment. Taken together, our study for the first time demonstrated an abnormal TRPV4-related mechanosensitive Ca2+ signaling in DCM-hiPSC-CMs.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Dilatada
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Cálcio
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Sinalização do Cálcio
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Citosol
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Miócitos Cardíacos
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Mecanotransdução Celular
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Canais de Cátion TRPV
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Células-Tronco Pluripotentes Induzidas
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article