Ethanol treatment (≥100 mg/dl) directly promotes cardiac fibroblast activation by stimulating TGF-β release, an effect that is attenuated by TGF-β inhibition.
Ethanol directly promotes cardiac fibroblast activation by stimulating TGF-β release, a process that can be attenuated by TGF-β inhibition, providing mechanistic insight into alcoholic cardiomyopathy.
BACKGROUND: Alcohol abuse is the second leading cause of dilated cardiomyopathy, a disorder specifically referred to as alcoholic cardiomyopathy (ACM). Rodent and human studies have revealed cardiac fibrosis to be a consequence of ACM, and prior studies by this laboratory have associated this occurrence with elevated transforming growth factor-beta (TGF-β) and activated fibroblasts (myofibroblasts). To date, there have been no other studies to investigate the direct effect of alcohol on the cardiac fibroblast. METHODS: Primary rat cardiac fibroblasts were cultured in the presence of ethanol (EtOH) and assayed for fibroblast activation by collagen gel contraction, alpha-smooth muscle actin (α-SMA) expression, migration, proliferation, apoptosis, collagen I and III, and TGF-β expression. The TGF-β receptor type 1 inhibitor compound SB 431542 and a soluble recombinant TGF-βII receptor (RbII) were used to assess the role of TGF-β in the response of cardiac fibroblasts to EtOH. RESULTS: Treatment for cardiac fibroblasts with EtOH at concentrations of 100 mg/dl or higher resulted in fibroblast activation and fibrogenic activity after 24 hours including an increase in contraction, α-SMA expression, migration, and expression of collagen I and TGF-β. No changes in fibroblast proliferation or apoptosis were observed. Inhibition of TGF-β by SB 431542 and RbII attenuated the EtOH-induced fibroblast activation. CONCLUSIONS: EtOH treatment directly promotes cardiac fibroblast activation by stimulating TGF-β release from fibroblasts. Inhibiting the action of TGF-β decreases the fibrogenic effect induced by EtOH treatment. The results of this study support TGF-β to be an important component in cardiac fibrosis induced by exposure to EtOH.
Law et al. (Mon,) conducted a other in Alcoholic cardiomyopathy. Ethanol (EtOH) and TGF-β inhibitors (SB 431542 and RbII) was evaluated on Fibroblast activation (collagen gel contraction, α-SMA expression, migration, proliferation, apoptosis, collagen I and III, and TGF-β expression). Ethanol treatment (≥100 mg/dl) directly promotes cardiac fibroblast activation by stimulating TGF-β release, an effect that is attenuated by TGF-β inhibition.
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