Neurotransmitter Metabolism by Monoamine Oxidase in Porcine Heart Differs by Location and is Increased with Obesity/Metabolic Syndrome

Abstract

Monoamine Oxidase (MAO), an outer mitochondrial enzyme, catalyzes the oxidative deamination of catecholamines and other biological amines, and in the process, produces a reactive aldehyde and H2O2. Our lab has recently shown that MAO activity (indirectly measured through H2O2 production) in right atrial myocardium of patients undergoing cardiac surgeries is associated with postoperative atrial fibrillation. Furthermore, our lab has shown that diabetic patients have higher MAO-A and -B content and rates of activity in this tissue, compared to nondiabetics. While recent studies have explored the connection between MAO and cardiac dysfunction, the chamber-specific content and activity of MAO within the heart is still unknown. Therefore, we characterized the regional enzymatic activity of MAO-A and -B based upon the hypothesis that the atria would have the highest MAO activity due to the greater density of local sympathetic nerve innervation in this region. For this study, porcine hearts were isolated from domestic pigs, as this model closely recapitulates the physiology of the human heart. One group of pigs were fed a high fat, high sucrose diet for 16 weeks to induce obesity/metabolic syndrome (n=4). Three MAO substrates (dopamine, norepinephrine, serotonin) and two isoform-selective inhibitors (clorgyline=MAO-A, deprenyl=MAO-B) were used to characterize MAO activities. Each enzyme content was measured using ELISA and confirmed with immunoblots. Kinetic analysis showed that, across all substrates, when normalized to tissue protein, the left atrium had the highest maximal MAO-A and –B activity while the other three chambers were similar. Furthermore, maximal MAO activity in the left ventricle of pigs with metabolic syndrome was greater than left ventricle of control group. Our findings suggest that MAO activity differs by location in the heart (i.e., chamber heterogeneity). Upon confirmation in human heart, this information is useful to inform about clinical pharmacology applications where MAO inhibitors might be used.