Modulation of Oxidative Stress in Heart Disease by Uncoupling Proteins

According to “free-radical theory” of disease, Reactive Oxygen Species (ROS) play a key role in the pathogenesis of several diseases including cardiovascular disease. When the balance between production of free radicals and antioxidant capacity of the cardiac cells is altered due to pathophysiological conditions, oxidative stress is induced. Oxidative stress has been linked to the development of ischemic heart disease, atherosclerosis, congestive heart failure, ischemic-reperfusion injury, and vascular endothelial dysfunction. In this context, antioxidant supplementation would have a positive effect on cardiovascular diseases. However, several clinical trials over the past decades employed different strategies of antioxidant therapies which have failed to achieve favorable results in ameliorating or preventing cardiovascular diseases. Much less attention has been paid to the modulation of ROS production, despite the fact that prevention, rather than cure, would appear to be a logic approach to attenuate the oxidative damage. This chapter intends to highlight the mechanisms of oxidative stress modulation – by Natural or induced mitochondrial uncoupling respiration – in regulating ROS production and its significance in cardiovascular pathophysiological conditions.