Monoamine Oxidase Is Overactivated in Left and Right Ventricles from Ischemic Hearts: An Intriguing Therapeutic
Maria Elena Manni1, Stefania Rigacci2, Elisabetta Borchi2
1Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Center of Molecular Medicine (CIMMBA), University of Florence, Florence, Italy.
Abstract:
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. However, little is known about MAO activity in human failing heart and its relationship with redox imbalance. Therefore, we measured MAO activity in the left (LV) and in the right (RV) ventricle of human nonfailing (NF) and in end-stage ischemic (IHD) and nonischemic failing hearts. We found that both MAO isoforms (MAO-A/B) significantly increased in terms of activity and expression levels only in IHD ventricles. Catalase and aldehyde dehydrogenase-2 activities (ALDH-2), both 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. Oxidative stress markers levels were significantly increased only in the failing RV. 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. This latter finding points to a possible pathogenic role of MAO-A in human myocardial failure supporting the idea that MAO-A could be a new therapeutic target in HF.
Insights
Monoamine oxidase (MAO) activity and reactive oxygen species (ROS) generation increase in human heart failure, particularly in ischemic heart disease. MAO-A linked to actin oxidation and dysfunction suggests it as a therapeutic target for heart failure.
Area of Science:
- Cardiology
- Biochemistry
- Molecular Biology
Background:
- Reactive oxygen species (ROS) are implicated in human heart failure (HF).
- Monoamine oxidase (MAO) is a potential source of ROS in cardiomyopathies.
- The role of MAO activity and redox imbalance in human failing hearts requires further investigation.
Purpose of the Study:
- To investigate MAO activity and its relationship with redox imbalance in human failing hearts.
- To compare MAO activity in ischemic heart disease (IHD) versus nonfailing (NF) hearts.
- To explore the link between MAO-A, actin oxidation, and ventricular dysfunction.
Main Methods:
- Measurement of MAO-A and MAO-B activity and expression in human left (LV) and right (RV) ventricles from NF, IHD, and failing hearts.
- Assessed activities of catalase and aldehyde dehydrogenase-2 (ALDH-2).
- Quantified oxidative stress markers and actin oxidation levels.
Main Results:
- Both MAO-A and MAO-B activities and expression were significantly elevated in IHD ventricles.
- Catalase and ALDH-2 activities increased in failing LV; ALDH-2 increased in failing RV.
- Increased oxidative stress markers and actin oxidation were observed in failing ventricles, linked to MAO-A activity.
Conclusions:
- MAO-A-dependent ROS generation is closely associated with actin oxidation and ventricular dysfunction in human heart failure.
- Elevated MAO activity, particularly MAO-A, may play a pathogenic role in human myocardial failure.
- MAO-A emerges as a potential therapeutic target for heart failure.
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