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 [3H]-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 [3H]-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 [3H]-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.

SLC41A1 knockdown inhibits angiotensin II-induced cardiac fibrosis by preventing Mg2+ efflux and Ca2+ signaling in cardiac fibroblasts

“…⁄ P < 0.05 vs. NC + Ang II. modulation of calcium channels and calcium related proteins have been reported to be beneficial to anti-fibrosis [39,40]. Experimental and clinical data have demonstrated that Mg 2+ deficiency can elicit the elevation of intracellular Ca 2+ concentrations, formation of oxygen radicals and pro-inflammatory agents and changes in membrane permeability as well as transport processes in cardiac cells [41,42].…”

Matrix metalloproteinase-2 stimulates collagen-I expression through phosphorylation of focal adhesion kinase in rat cardiac fibroblasts

“…Transfection of cardiac fibroblasts with small interfering RNA (siRNA) was performed as previously described (20). The silencer predesigned siRNA against MMP-2 (s135546; Life Technologies, Carlsbad, CA) was synthesized according to rat-specific sequences.…”

Transient Receptor Potential Melastatin 7 (TRPM7) Contributes to H2O2-Induced Cardiac Fibrosis via Mediating Ca2+ Influx and Extracellular Signal–Regulated Kinase 1/2 (ERK1/2) Activation in Cardiac Fibroblasts

“…-related protein has been reported have antifibrosis effects (28,29). Although the expression of some TRP channels can be detected by using RT-PCR and appears to be associated with cardiac fibrosis, many of them cannot be detected by using electrophysiological recordings (6,30).…”