Monoamine oxidase inhibition improves vascular function in mammary arteries from nondiabetic and diabetic patients with coronary heart disease.

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.

Healing Potential of the Anterior Cruciate Ligament Remnant Stump.

AIM: The aim of this study was to analyze the microstructural architecture and cellular differentiation of the anterior cruciate ligament (ACL) stumps in different stages after injury, as this could augment graft biointegration. MATERIALS AND METHODS: The histological appearance and immunoreaction for cluster of differentiation 34 antigen (CD34) of 54 biopsies from 27 remnants were compared to 10 biopsies from 5 normal cruciate ligaments. RESULTS: CD34 reaction in endothelial cells, fibroblasts and fibrocytes was consistently positive in small synovial vessels. Remnants also exhibited CD34(+) cells among collagen fibers. Blood vessel density varied between specimens. The mean vascular microdensity was 43 per ×200 field in remnants compared to 15.2 in controls. A total of 94.44% of remnant ACL samples had significant hyperplasia of stellate and fusiform stromal cells, CD34(+); 22.4% had developed capillary vessels inside the ligament; 33% exhibited ongoing angiogenesis. CONCLUSION: Significant differences exist between torn and intact ACL regarding microvascularization. The remnants contain stellate stromal cells and CD34(+) fibrocytes, and display angiogenesis both at synovia as well as in the ligament itself. These findings underline the potential contribution to neoligament healing when remnants are preserved.

Monoamine Oxidases as Potential Contributors to Oxidative Stress in Diabetes: Time for a Study in Patients Undergoing Heart Surgery.

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.