Effect of efonidipine on TGF-ß1-induced cardiac fibrosis through Smad2-dependent pathway in rat cardiac fibroblasts.
J Pharmacol Sci
; 117(2): 98-105, 2011.
Article
em En
| MEDLINE
| ID: mdl-21897055
ABSTRACT
Transforming growth factor beta-1 (TGF-ß1) plays a critical role in progression of cardiac fibrosis, which may involve intracellular calcium change. We examined effects of efonidipine, a dual T-type and L-type calcium channel blocker (CCB), on TGF-ß1-induced fibrotic changes in neonatal rat cardiac fibroblast. T-type and L-type calcium channel mRNAs were highly expressed in cultured cardiac fibroblasts. TGF-ß1 (5 ng/mL) significantly increased Smad2 phosphorylation and [(3)H]-leucine incorporation, which were attenuated by pretreatment with efonidipine (10 µM). Neither R(-)efonidipine (10 µM), selective T-type CCB, nor nifedipine (10 µM), selective L-type CCB, efficaciously inhibited both TGF-ß1-induced Smad2 phosphorylation and [(3)H]-leucine incorporation. However, both were markedly attenuated by combination of R(-)efonidipine and nifedipine, EDTA, or calcium-free medium. Pretreatment with Smad2 siRNA significantly attenuated [(3)H]-leucine incorporation induced by TGF-ß1. These data suggest that efonidipine elicits inhibitory effects on TGF-ß1- and Smad2-dependent protein synthesis through both T-type and L-type calcium channel-blocking actions in cardiac fibroblasts.
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Base de dados:
MEDLINE
Assunto principal:
Di-Hidropiridinas
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Bloqueadores dos Canais de Cálcio
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Canais de Cálcio Tipo L
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Canais de Cálcio Tipo T
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Proteína Smad2
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Fator de Crescimento Transformador beta1
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Fibroblastos
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Nitrofenóis
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article