Assessment of Mitochondrial Dysfunction and Monoamine Oxidase Contribution to Oxidative Stress in Human Diabetic Hearts

Abstract

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.

Oxidative Stress and Cardiovascular Risk: Obesity, Diabetes, Smoking, and Pollution

“…MAO-A shows greater activity in diabetic cardiomyocytes, and MAO-A inhibition results in improved contractile function in preclinical DM models, despite persistent hyperglycemia and hyperlipidemia (71). However, no difference in MAO expression or MAO-related oxidative stress was recently observed in right atrial appendages from cardiac surgery patients with or without DM (72). …”

The Role of Oxidative Stress in Common Risk Factors and Mechanisms of Cardio-Cerebrovascular Ischemia and Depression

“…In heart disease, a clinical trial enrolling 3766 adults with prevalent diabetes mellitus illustrated that increased levels of 8-oxo-2′-deoxyguanosine, a biomarker of oxidative DNA damage, were independently associated with elevated cardiovascular mortality [91]. In depression, recent studies have proposed that one possible mechanism linking diabetes and depression was the increase in lipid peroxidation and decrease in antioxidant activity in the hippocampal and prefrontal cortices, which are the areas of the brain associated with mood [92,93]. (Figure 1 C).…”

Assessment of Platelet Respiration as Emerging Biomarker of Disease

“…Hematologic malignancies (HM) are tumours of hematopoietic and lymphoid tissues that include leukemias, lymphomas, and plasma cell neoplasms (multiple myeloma). Even though the general tendency of HM survival rates has slightly increased over the past decade due to treatment advances (Dunham-Snary et al 2014), these diseases represent the fourth most common type of cancer in both male and female populations (Caimari et al 2010). In this context, a biomarker that can be correlated with the evolution, progression, severity and treatment response, might be advantageous in HM monitoring and therapy.…”