Monoamine oxidase contributes to the metabolic memory in diabetic mice

Abstract

Monoamine oxidase (MAO) with 2 isoforms, A and B, are mitochondrial enzymes that recently emerged as important cardiovascular sources of reactive oxygen species. The aim of the present study was to assess the contribution of monoamine oxidase (MAO) to the “metabolic memory” phenomenon, as mechanism underlying the persistent oxidative damage and endothelial dysfunction in an experimental model of diabetes mellitus in mice. We hypothesized that: (i) MAO is an important contributor to vascular oxidative stress, in context of diabetes, even after glucose normalisation and (ii) selective MAO-A and MAO-B inhibition (clorgyline and selegiline, 1 mg/kg/day, 1 week) will reduce oxidative stress and improve vascular reactivity. Our results showed that: (i) MAOs expression increased in mice aortas (assessed by qRT-PCR and immune fluorescence) after 2 weeks of hyperglycemia together with high ROS generation (assessed by spectophotometry and confocal microscopy – DHE staining) and impaired vascular relaxation, (ii) glucose normalization (glargine, 10 U/kg/day, 1 week) did not significantly reduced ROS generation, and (iii) in vivo administration of MAO inhibitors (in addition to insulin) reduced ROS levels and improved vascular relaxation in diabetic mice. In conclusion, MAOs represent a potential therapeutic target for vascular diabetic complications. MAO inhibitors are viable candidates for drug repurposing as vasculo-protective agents in diabetes. Research supported by the university internal grant code 6POSTDOC/1871/12.02.2020.