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College of Engineering and Computing


Biomedical Engineering

Alcohol-induced Myocardial Fibroblast Activation and Fibrosis

Chronic alcohol abuse contributes to over sixty disease conditions and deleterious remodeling of most organs.  Tissue fibrosis, or accumulation of excessive extracellular matrix components, accompanies alcohol-induced remodeling in many organs.  In the heart, alcohol abuse results in death of heart myocytes and activation of myocardial fibroblasts leading to fibrosis.  Continued abuse of alcohol results in a condition termed alcoholic cardiomyopathy and eventually heart failure.  Approximately one-third of all alcoholics will develop alcoholic cardiomyopathy. The molecular mechanisms of alcohol-induced myocardial fibrosis and heart failure have not been established.  Research from our laboratory has illustrated that exposure of isolated heart fibroblasts to alcohol results in activation to a myofibroblast phenotype characterized by enhanced expression of extracellular matrix components.  Our research has illustrated that fibroblast activation is at least in part due to the autocrine/paracrine effects of transforming growth factor-beta.  Ongoing research in our lab is focused on understanding how chronic exposure to alcohol results in increased production of this potent profibrotic growth factor.  Preliminary studies have illustrated that alcohol-induced oxidative stress may be an important mediator of this process.

Publications

•  Law BA, Fix C, Barton B, Carver W (2015) Role of mast cells in alcohol-induced tissue damage and remodeling.  Int J Clin Exp Pathol May:2015.

•  Law BA, Carver WE (2013) Activation of cardiac fibroblasts by ethanol is blocked by TGF-β inhibition. Alcohol Clin Exp Res 37:1286-1294.

•  Law BA, Levick SP, Carver WE (2012) Alterations in cardiac structure and function in a murine model of chronic alcohol consumption. Microsc Microanal 18:453-461.