Despite extensive knowledge of the deleterious effects of chronic alcohol abuse, alcoholism and its associated health issues remain a substantial problem. Approximately 14 million individuals in the United States alone battle alcohol addiction. Alcohol dependence and abuse result in over 200 billion dollars in health care costs annually in the United States. Chronic alcohol abuse results in damage to most organs and contributes to over 60 diseases. Extensive research has shown that liver and pancreas disease in response to alcohol abuse involves excessive accumulation of connective tissue or fibrosis. In these organs, resident stellate cells (and likely other cell populations like bone marrow-derived cells) are transformed into myofibroblasts, which actively participate in tissue remodeling through the secretion of extracellular matrix proteins. It appears that persistent inflammation induced by excessive alcohol consumption plays a role in the formation of myofibroblasts and subsequent fibrosis. Long-term alcohol abuse also leads to heart disease termed alcoholic cardiomyopathy. Much less is known about the progression of alcohol damage in the heart compared to that in many other organs. It is clear that alcohol and its metabolites can directly affect the function of cardiac muscle cells. The contribution of other cell types to the damaging effects of alcohol on the heart is not clear. We propose that chronic alcohol abuse elicits an adaptive response that includes cardiac hypertrophy (growth), fibrosis and inflammation. This initially adaptive response eventually results in decompensation of the heart with the ultimate consequence being that the heart is unable to meet the demands of the body. The long-term goal of the proposed study is to elucidate the mechanisms whereby chronic alcohol abuse results in alcoholic cardiomyopathy.
The aim of the present study is to utilize a cell culture system to determine the effects of alcohol exposure on heart fibroblasts and inflammatory cells. These studies will provide important new information regarding the response of the heart and its cells to alcohol. These studies will also provide an excellent venue for the training of the principal investigator in molecular, cellular and whole animal techniques needed to investigate the mechanisms of alcohol-induced tissue damage.
Chronic alcohol abuse is a major health issue in the United States and most other countries. Alcohol abuse damages most organ systems in the body and directly or indirectly is associated with numerous disease conditions. Alcohol remains somewhat of a paradox in the cardiovascular system as low levels of alcohol appear to be beneficial and protect against cardiovascular disease, while higher levels lead to a disease called alcoholic cardiomyopathy. The proposed studies will examine the effects of chronic alcohol abuse on heart structure and function. These studies will provide important insight into the effects of alcohol on the heart and will provide the foundations for Brittany Law's PhD training.
| Law, Brittany A; Carver, Wayne E (2013) Activation of cardiac fibroblasts by ethanol is blocked by TGF-? inhibition. Alcohol Clin Exp Res 37:1286-94 |
