Monoamine oxidase-A, serotonin and norepinephrine: synergistic players in cardiac physiology and pathology.

ABSTRACT

The mitochondrial enzyme monoamine oxidase A (MAO-A) is widely distributed in neuronal, myocyte and non-myocyte cardiac compartments. After the demonstrations that both cardiac neuronal and extraneuronal MAO-A contribute to the degradation of norepinephrine and serotonin, several studies attempted to determine the impact of MAO-A activity in the control of local concentration of the two biogenic amines and in their receptor-mediated effects. From the 2000s, an additional mechanism of action of MAO-A has been proposed. Such mechanism involves hydrogen peroxide (H2O2) production during substrate degradation. This finding stimulated a growing interest on the role of MAO-A-dependent oxidative stress in cardiac pathophysiology. Altogether, the results obtained by different groups showed that MAO-A played a key role in the regulation of physiological cardiac function and in the development of acute and chronic heart diseases through two mechanisms the regulation of substrate concentrations and the intracellular production of reactive oxygen species. In this review, we will give an overview of the major results on the role of MAO-A in the field of cardiac diseases.