The Role of Oxidative Stress and Apoptosis in the Pathogenesis of Heart Failure
Apoptotic cell death has been implicated in cardiovascular pathologies such as congestive heart failure, myocardial ischemia, cardiomyopathy and atherogenesis. A growing body of literature suggests apoptosis induced by oxidative stress plays a key role in the pathogenesis of heart failure. Our preliminary results suggest that there is increased expression of antiapoptotic Bcl-2 proteins and decreased expression of antiapoptotic protein Mcl-1 in ischemic heart disease patients as compared to the control group. This increase in Bcl-2 expression is accompanied by a decrease in expression of proapoptotic Bax proteins when compared to controls. We believe that irrespective of proapoptotic or antiapoptotic protein influences, the ratio of Bcl-2/Bax proteins plays a major role in determining cardiomyocyte apoptosis. An enhanced Bcl-2 expression in ischemic heart disease patients suggests a possible compensatory mechanism of cell protection. The precise trigger of the apoptotic process in cardiomyocytes is not yet clear but our preliminary data suggest that apoptosis and oxidative stress may play a critical role. It is plausible that alterations caused by reactive oxygen species (ROS) in the molecular functions of cellular structures may contribute to ischemia, apoptosis and ultimately to heart failure. Further studies are required to establish a possible link between oxidative stress and apoptosis. The conclusive evidence and precise mechanism of apoptosis in the pathogenesis of ischemic heart disease may open abundant therapeutic avenues to prevent cardiac dysfunction.