Methylene blue reduces monoamine oxidase expression and oxidative stress in human cardiovascular adipose tissue.

Cardiovascular diseases represent the major cause of morbidity mainly due to chronic heart failure. Epicardial (EAT) and perivascular adipose tissues (PVAT) are considered major contributors to the pathogenesis of cardiometabolic pathologies. Monoamine oxidases (MAOs) are mitochondrial enzymes recognized as sources of reactive oxygen species (ROS) in cardiometabolic pathologies. Methylene blue (MB) is one of the oldest protective agents, yet no data are available about its effects on adipose tissue. The present pilot study was aimed at assessing the effects of MB: (i) on MAO expression and (ii) oxidative stress in EAT and PVAT harvested from patients with heart failure subjected to cardiac surgery (n = 25). Adipose tissue samples were incubated with MB (0.1 µM/24 h) and used for the assessment of MAO gene and protein expression (qPCS and immune fluorescence) and ROS production (confocal microscopy and spectrophotometry). The human cardiovascular adipose tissues contain both MAO isoforms, predominantly MAO-A. Incubation with MB reduced MAOs expression and oxidative stress; co-incubation with serotonin, the MAO-A substrate, further augmented ROS generation, an effect partially reversed by MB. In conclusion, MAO-A is the major isoform expressed in EAT and PVAT and contribute to local oxidative stress; both effects can be mitigated by methylene blue.

Monoamine oxidase is a source of cardiac oxidative stress in obese rats: the beneficial role of metformin.

Diet-induced metabolic diseases, such as obesity, metabolic syndrome, and type 2 diabetes (T2DM) are the global threatening epidemics that share cardiovascular oxidative stress as common denominator. Monoamine oxidase (MAO) has recently emerged as a constant source of reactive oxygen species (ROS) in DM. Metformin, the first-line drug in T2DM, elicits cardiovascular protection via pleiotropic effects. The present study was aimed to assess the contribution of MAO to the early cardiac oxidative stress in a rat model of high-calorie junk food (HCJF) diet-induced obesity and prediabetes and whether metformin can alleviate it. After 6 months of HCJF, rats developed obesity and hyperglycemia. Hearts were isolated and used for the evaluation of MAO expression and ROS production. Experiments were performed in the presence vs absence of metformin (10 µM) and MAO-A and B inhibitors (clorgyline and selegiline, 10 µM), respectively. Both MAO isoforms were overexpressed and led to increased ROS generation in cardiac samples harvested from the obese animals. Acute treatment with metformin and MAO inhibitors was able to mitigate oxidative stress. More important, metformin downregulated MAO expression in the diseased samples. In conclusion, MAO contributes to oxidative stress in experimental obesity and can be targeted with metformin.

Metformin and empagliflozin modulate monoamine oxidase-related oxidative stress and improve vascular function in human mammary arteries.

Monoamine oxidases (MAOs), mitochondrial enzymes with two isoforms, A and B, have been recently recognized as significant contributors to oxidative stress in the cardiovascular system. The present study was purported to assess the effect of metformin and empagliflozin on MAO expression, oxidative stress and vascular reactivity in internal mammary arteries harvested from overweight patients with coronary heart disease subjected to bypass grafting. Vascular rings were prepared and acutely incubated (12 h) with high glucose (GLUC, 400 mg/dL) or angiotensin II (AII, 100 nM) and metformin (10 µM) and/or empagliflozin (10 µM) and used for the assessment of MAO expression (qRT-PCR and immune histochemistry), reactive oxygen species (ROS, confocal microscopy and spectrophotometry), and vasomotor function (myograph). Ex vivo stimulation with GLUC or AII increased both MAOs expression, ROS production and impaired relaxation to acetylcholine (ACh) of the vascular rings. All effects were alleviated by incubation with each antidiabetic drug; no cumulative effect was obtained when the drugs were applied together. In conclusion, MAO-A and B are upregulated in mammary arteries after acute stimulation with GLUC and AII. Endothelial dysfunction and oxidative stress were alleviated by either metformin or empagliflozin in both stimulated and non-stimulated vascular samples harvested from overweight cardiac patients.