Activation of Cardiac Fibroblasts by Ethanol Is Blocked by TGF-β Inhibition
Article first published online: 25 MAR 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 8, pages 1286–1294, August 2013
How to Cite
Law, B. A. and Carver, W. E. (2013), Activation of Cardiac Fibroblasts by Ethanol Is Blocked by TGF-β Inhibition. Alcoholism: Clinical and Experimental Research, 37: 1286–1294. doi: 10.1111/acer.12111
- Issue published online: 26 JUL 2013
- Article first published online: 25 MAR 2013
- Manuscript Accepted: 9 JAN 2013
- Manuscript Received: 12 SEP 2012
- NIH. Grant Numbers: HL083441, F31AA020162
- Cardiac Fibrosis;
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.
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.
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.
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.