Nicotine Induces Cardiomyocyte Hypertrophy Through TRPC3-Mediated Ca2+/NFAT Signalling Pathway.
Can J Cardiol
; 32(10): 1260.e1-1260.e10, 2016 10.
Article
em En
| MEDLINE
| ID: mdl-26952156
ABSTRACT
BACKGROUND:
Nicotine is thought to be an important risk factor for the development of cardiovascular diseases. However, the effects of nicotine on cardiomyocyte hypertrophy are poorly understood. The present study was designed to explore the role of nicotine in cardiomyocyte hypertrophy and its underlying mechanism.METHODS:
We used primary cardiomyocytes isolated from Wistar rats to examine the effects of nicotine on intracellular Ca2+ mobilization and hypertrophy determined by immunofluorescence, quantitative polymerase chain reaction, and western blot analysis. A luciferase reporter assay was used to examine the activity of NFAT signalling.RESULTS:
We found that nicotine caused cardiomyocyte hypertrophy, which was accompanied by increased intracellular Ca2+. Nicotine-enhanced intracellular Ca2+ concentration ([Ca2+]i) was significantly abolished by store-operated Ca2+ entry (SOCE) and TRPC inhibitors. Knockdown of TRPC3 significantly decreased nicotine-induced SOCE and hypertrophy. Moreover, calcineurin-nuclear factor of activated T cells (NFAT) is involved in TRPC3-mediated Ca2+ signalling and cardiomyocyte hypertrophy. Notably, upregulation of TRPC3 by nicotine requires TRPC3-mediated Ca2+ influx and calcineurin-NFAT signalling activation.CONCLUSIONS:
Our findings demonstrate that the prohypertrophic effect of nicotine on cardiomyocytes is dependent on enhanced TRPC3 expression through a calcium-dependent regulatory loop, which could become a potential target for prevention and treatment of cardiac hypertrophy.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Miócitos Cardíacos
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Crescimento Celular
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Canais de Cátion TRPC
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Fatores de Transcrição NFATC
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Estimulantes Ganglionares
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Nicotina
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article