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.
- 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.