Alcohol is a major public health concern in the United States due to the various well-documented pathological conditions associated with its use and abuse. Alcohol-induced heart disease is responsible for significant amount of morbidity and mortality in alcoholics, however, the understanding of many of the underlying molecular mechanisms remains elusive. The goal of this study is to test the hypotheses that 1) uncoupling protein-2 (UCP2) expression and activity has direct consequences which contribute to decreased myocardial contractility and the development of heart failure in alcoholic cardiomyopathy (ACM), 2) oxidative damage due to generation of excess reactive oxygen species (ROS) contributes to disease onset and progression, and UCP2 expression is induced in an effort to dampen ROS generation and to prevent further oxidative damage, and 3) this adaptive change leading to UCP2 expression leads to decreased ATP production, thus hindering various ATP-dependent cellular processes and ultimately contributing to compromised myocardial function and heart failure.
| Turner, Jay D; Gaspers, Lawrence D; Wang, Guoqiang et al. (2010) Uncoupling protein-2 modulates myocardial excitation-contraction coupling. Circ Res 106:730-8 |
