Increased Reactive Oxygen Species Production and Functional Alterations in Antioxidant Enzymes in Human Failing Myocardium

The decrease in MnSOD activity in failing myocardium, in the setting of increased mRNA expression, may reflect decreased translation or processing, or a posttranslational modification of MnSOD. The increase in MnSOD mRNA in failing hearts is consistent with the thesis that there is increased oxidative stress in failing myocardium that leads to increase transcription of antioxidant enzymes. The source of this direct measure of ROS is likely superoxide. These observations have implications for the pathophysiology and treatment of heart failure.