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Activation of Cardiac Fibroblasts by Ethanol Is Blocked by TGF ‐β Inhibition
Author(s) -
Law Brittany A.,
Carver Wayne E.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12111
Subject(s) - ethanol , transforming growth factor , chemistry , microbiology and biotechnology , pharmacology , medicine , biology , biochemistry
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 ( E t OH ) 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 ‐β II receptor (Rb II ) were used to assess the role of TGF ‐β in the response of cardiac fibroblasts to E t OH . Results Treatment for cardiac fibroblasts with E t OH 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 Rb II attenuated the E t OH ‐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 E t OH treatment. The results of this study support TGF ‐β to be an important component in cardiac fibrosis induced by exposure to E t OH .