title: Effect of efonidipine on TGF-β1-induced cardiac fibrosis through Smad2-dependent pathway in rat cardiac fibroblasts.
abstract: Transforming growth factor beta-1 (TGF-β1) 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-β1-induced fibrotic changes in neonatal rat cardiac fibroblast. T-type and L-type calcium channel mRNAs were highly expressed in cultured cardiac fibroblasts. TGF-β1 (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-β1-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-β1. These data suggest that efonidipine elicits inhibitory effects on TGF-β1- and Smad2-dependent protein synthesis through both T-type and L-type calcium channel-blocking actions in cardiac fibroblasts.
authors: Department of Pharmacology, Faculty of Medicine, Kagawa University, Japan.
authors: Bai
authors: B
authors: Lei
authors: Hirofumi
authors: H
authors: Hitomi
authors: Tatsuhiko
authors: T
authors: Mori
authors: Yukiko
authors: Y
authors: Nagai
authors: Kazushi
authors: K
authors: Deguchi
authors: Hirohito
authors: H
authors: Mori
authors: Tsutomu
authors: T
authors: Masaki
authors: Daisuke
authors: D
authors: Nakano
authors: Hiroyuki
authors: H
authors: Kobori
authors: Yasushi
authors: Y
authors: Kitaura
authors: Akira
authors: A
authors: Nishiyama
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009543:Nifedipine / Q000494:pharmacology; D009596:Nitrophenols / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D034741:RNA, Small Interfering; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D053773:Transforming Growth Factor beta1; C066425:efonidipine; D009543:Nifedipine