Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide (H₂O₂) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators of endothelial dysfunction in DM is unknown, and so we studied this in a streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein) was increased in both arterial samples and hearts isolated from the diabetic animals. Also, H₂O₂ production (ferrous oxidation – xylenol orange assay) in aortic samples was significantly increased, together with an impairment of endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline and selegiline) attenuated ROS production by 50% and partially normalized the endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in particular the MAO-B isoform, are induced in aortas and hearts in the streptozotocin-induced diabetic rat model and contribute, via the generation of H₂O₂, to the endothelial dysfunction associated with experimental diabetes.

Mitochondria‐related oxidative stress is a pathomechanism causally linked to coronary heart disease (CHD) and diabetes mellitus (DM). Recently, mitochondrial monoamine oxidases (MAOs) have emerged as novel sources of oxidative stress in the cardiovascular system and experimental diabetes. The present study was purported to assess the mitochondrial impairment and the contribution of MAOs‐related oxidative stress to the cardiovascular dysfunction in coronary patients with/without DM. Right atrial appendages were obtained from 75 patients randomized into 3 groups: (1) Control (CTRL), valvular patients without CHD; (2) CHD, patients with confirmed CHD; and (3) CHD‐DM, patients with CHD and DM. Mitochondrial respiration was measured by high‐resolution respirometry and MAOs expression was evaluated by RT‐PCR and immunohistochemistry. Hydrogen peroxide (H₂O₂) emission was assessed by confocal microscopy and spectrophotometrically. The impairment of mitochondrial respiration was substrate‐independent in CHD‐DM group. MAOs expression was comparable among the groups, with the predominance of MAO‐B isoform but no significant differences regarding oxidative stress were detected by either method. Incubation of atrial samples with MAOs inhibitors significantly reduced the H₂O₂ in all groups. In conclusion, abnormal mitochondrial respiration occurs in CHD and is more severe in DM and MAOs contribute to oxidative stress in human diseased hearts with/without DM.

Monoamine oxidases (MAOs) are mitochondrial enzymes with 2 isoforms that have emerged as important contributors to cardiovascular oxidative stress via the constant generation of hydrogen peroxide. The present study was purported to assess whether MAO-derived H₂O₂ contributes to the endothelial dysfunction in mammary arteries harvested from coronary heart disease patients with and without diabetes mellitus subjected to coronary artery bypass grafting. To this aim, the effects of MAO inhibition on vascular contractility to phenylephrine and endothelial-dependent relaxation (EDR) in response to acetylcholine were studied in vascular segments. Clorgyline (irreversible MAO-A inhibitor), selegiline (irreversible MAO-B inhibitor), and moclobemide (reversible MAO-A inhibitor) were applied in the organ bath (10 μmol/L). MAO expression was assessed by immunohistochemistry. We found a constant impairment of EDR that has been significantly attenuated in the presence of the MAO-A and MAO-B inhibitors in both groups of coronary heart disease patients. MAO-B was the dominant isoform in all human diseased vessels. In conclusion, in vitro inhibition of MAO significantly improved EDR in human mammary arteries, regardless of the presence of diabetes. These data suggest that MAO inhibitors might be useful in restoring endothelial response in clinical conditions associated with increased oxidative stress, such as coronary artery disease and diabetes.

Introduction: A renal biopsy represents the gold standard in the diagnosis, prognosis, and management of patients with glomerulonephritis. So far, non-invasive elastographic techniques have not confirmed their utility in replacing a biopsy; however, the new and improved software from Hologic Supersonic Mach 30 is a promising method for assessing the renal tissue’s stiffness and viscosity. We investigated whether this elastography technique could reveal renal tissue fibrosis in patients with chronic glomerulonephritis. Materials and methods: Two-dimensional-shear wave elastography (SWE) PLUS and viscosity plane-wave ultrasound (Vi PLUS) assessments were performed in 40 patients with chronic glomerulopathies before being referred for a renal biopsy. For each kidney, the mean values of five stiffness and viscosity measures were compared with the demographic, biological, and histopathological parameters of the patients. Results: In total, 26 men and 14 women with a mean age of 52.35 ± 15.54 years, a mean estimated glomerular filtration rate (eGFR) of 53.8 ± 35.49 mL/min/1.73m², and a mean proteinuria of 6.39 ± 7.42 g/24 h were included after providing their informed consent. Out of 40 kidney biopsies, 2 were uninterpretable with inappropriate material and were divided into four subgroups based on their fibrosis percentage. Even though these elastography techniques were unable to differentiate between separate fibrosis stages, when predicting between the fibrosis and no-fibrosis group, we found a cut-off value of <20.77 kPa with the area under the curve (AUC) of 0.860, a p < 0.001 with 88.89% sensitivity, and a 75% specificity for the 2D SWE PLUS measures and a cut-off value of <2.8 Pa.s with an AUC of 0.792, a p < 0.001 with 94% sensitivity, and a 60% specificity for the Vi PLUS measures. We also found a cut-off value of <19.75 kPa for the 2D SWE PLUS measures (with an AUC of 0.789, p = 0.0001 with 100% sensitivity, and a 74.29% specificity) and a cut-off value of <1.28 Pa.s for the Vi PLUS measures (with an AUC 0.829, p = 0.0019 with 60% sensitivity, and a 94.29% specificity) differentiating between patients with over 40% fibrosis and those with under 40%. We also discovered a positive correlation between the glomerular filtration rate (eGFR) and 2D-SWE PLUS values (r = 0.7065, p < 0.0001) and Vi PLUS values (r = 0.3637, p < 0.0211). C reactive protein (CRP) correlates with the Vi PLUS measures (r = −0.3695, p = 0.0189) but not with the 2D SWE PLUS measures (r = −0.2431, p = 0.1306). Conclusion: Our findings indicate that this novel elastography method can distinguish between individuals with different stages of renal fibrosis, correlate with the renal function and inflammation, and are easy to use and reproducible, but further research is needed for them to be employed routinely in clinical practice.

Oxidative stress is a pathomechanism causally linked to the progression of chronic cardiovascular diseases and diabetes. Mitochondria have emerged as the most relevant source of reactive oxygen species, the major culprit being classically considered the respiratory chain at the inner mitochondrial membrane. In the past decade, several experimental studies unequivocally demonstrated the contribution of monoamine oxidases (MAOs) at the outer mitochondrial membrane to the maladaptative ventricular hypertrophy and endothelial dysfunction. This paper addresses the contribution of mitochondrial dysfunction to the pathogenesis of heart failure and diabetes together with the mounting evidence for an emerging role of MAO inhibition as putative cardioprotective strategy in both conditions.