Monoamine oxidase is over-activated in left and right ventricles from ischemic hearts: an intriguing therapeutic target.

Growing evidence indicates that reactive oxygen species (ROS) may play a key role in human heart failure (HF). Monoamine oxidase (MAO) is emerging as a major ROS source in several cardiomyopathies. Therefore, we measured MAO activity in the left (LV) and in the right (RV) ventricle of human non failing (NF) and in end-stage ischemic (IHD) and non-ischemic failing hearts. We found that MAO activity significantly increased only in IHD ventricles as for the activity and the expression levels of both MAO isoforms (MAO-A and B). The activities of catalase and aldehyde dehydrogenase-2 (ALDH-2), implicated in MAO catalyzed catecholamine catabolism , were significantly elevated in the failing LV, whereas in the RV statistical significance was observed only for ALDH-2. The amounts of the oxidative stress markers malonyldialdeyde and carbonylated proteins, were significantly increased only in the failing RV. In addition, actin oxidation was significantly elevated in both failing ventricles and related to MAO-A activity and to functional parameters. These data suggest a close association between MAO-A-dependent ROS generation, actin oxidation and ventricular dysfunction. These data point to a possible pathogenic role of MAO-A in human myocardial failure and support the idea that MAO-A can be a new promising therapeutic target in HF.