Monoamine oxidase activity in end-stage heart failure associated with dilated and ischemic cardiomyopathies: a comparison between left and right ventricles

Dilated (DCM) and ischemic (IHD) cardiomyopathies are the most common causes of heart failure, which is characterized by a progressive remodeling and dysfunction. Reactive species (ROS) contributed to each of these abnormalities. Among the multiple source of ROS, the monoamine oxidases (MAOs), that catalyze oxidative deamination of catecholamines and biogenic amines. generating hydrogen peroxide (H2O2) and aldehyde, may play an important role in the maladaptive evolution towards failure. At homeostatic conditions, the amount of aldehydes and H2O2 are regulated by aldehyde dehydrogenase (ALDH) and catalase (CAT) activities, respectively, both rescuing enzymes of the heart. Possibly, different levels of such enzymes might be present in DMC and IHD failing hearts and they may be proposed as discriminating markers of the two cardiomyopathies. Therefore, we investigated the enzymatic activities of MAO-A and MAO-B, of cytosolic and mitochondrial ALDH and of CAT and the amount of carbonylated proteins and malondialdehyde (MDA), indirect markers of oxidative stress, in right (RV) and left ventricles (LV) from end-stage failing hearts secondary to IHD and DMC. Methods: MAO activity was measured radiochemically, using specific substrates for MAO-A and MAO-B isoforms in the presence of semicarbazide, inhibitor of other amine oxidases. CAT and ALDH activities were determined spectrophotometrically. MDA and carbonylated proteins levels were assayed using specific kits. Results: Both MAO isoforms were detected in failing hearts, with a total MAO activity ten times higher in IHD than in DMC. Interestingly, the activity of MAO-A, the more representative isoform, was similar in LV and RV for IHD but it was higher in LV (0.74±0.18) than in RV (0.32±0.12; p<0.05) for DCM, with no differences in MAO-B activity. On the other hand, CAT activity was significantly increased in LV (27.53±1.94; p<0.05) compared to RV (17.18±3.52), only for DMC. The same hearts showed MDA levels significantly enhanced in RV (3.51±0.44), compared to LV (2.70±0.45). No differences were observed in total ALDH activity and in the content of carbonylated protein. Conclusion: Both MAO isoforms, with a prevalence of MAO-A, were observed in failing hearts. Nevertheless, we reported a significant increase in total MAO activity in IHD compared to DCM. In DMC specimens MAO-A was preferentially active in LV compared to RV, in concomitance with a higher level of CAT activity and a lower level of MDA amount, suggesting a role for CAT in scavenging MAO-derived H2O2. Our results indicate that the evaluation of MAO activity, in particular MAO-A, might help to discriminate between IHD and DCM associated with heart failure.