Department of Functional Sciences III, Discipline of Pathophysiology, Center for Translational Research and Systems Medicine, "Victor Babeș" University of Medicine and Pharmacy Timişoara, Romania, Eftimie Murgu Sq., no. 2, 300041, Timișoara, Romania.
Department of Internal Medicine VII, Discipline of Diabetes, Nutrition and Metabolic Diseases, "Victor Babeș" University of Medicine and Pharmacy Timișoara, Romania, Eftimie Murgu Sq., no. 2, 300041, Timișoara, Romania.
Mol Cell Biochem. 2021 Nov;476(11):4019-4029. doi: 10.1007/s11010-021-04194-2. Epub 2021 Jul 3.
In the past decade, monoamine oxidase (MAO) with 2 isoforms, MAO-A and B, has emerged as an important source of mitochondrial reactive oxygen species (ROS) in cardio-metabolic pathologies. We have previously reported that MAO-related oxidative stress mediates endothelial dysfunction in rodent models of diabetes and diabetic patients; however, the role of MAO in the vascular impairment associated to obesity has not been investigated so far. Metformin (METF), the first-line drug in the therapy of type 2 diabetes mellitus, has been reported to elicit vasculoprotective effects via partially elucidated mechanisms. The present study was purported to assess the effects of METF on MAO expression, ROS production and vasomotor function of aortas isolated from rats with diet-induced obesity. After 24 weeks of high calorie junk food (HCJF) diet, isolated aortic rings were prepared and treated with METF (10 μM, 12 h incubation). Measurements of MAO expression (quantitative PCR and immune histochemistry), ROS production (spectrometry and immune-fluorescence) and vascular reactivity (myograph studies) were performed in rat aortic rings. MAO expression was upregulated in aortic rings isolated from obese rats together with an increase in ROS production and an impairment of vascular reactivity. METF decreased MAO expression and ROS generation, reduced vascular contractility and improved the endothelium-dependent relaxation in the diseased vascular preparations. In conclusion, METF elicited vascular protective effects via the mitigation of MAO-related oxidative stress in the rat model of diet-induced obesity.
在过去的十年中，单胺氧化酶（MAO）有 2 种同工酶，MAO-A 和 B，已成为心脏代谢病理中线粒体活性氧（ROS）的重要来源。我们之前报道过，MAO 相关的氧化应激在糖尿病啮齿动物模型和糖尿病患者中介导内皮功能障碍；然而，迄今为止，尚未研究 MAO 在与肥胖相关的血管损伤中的作用。二甲双胍（METF）是治疗 2 型糖尿病的一线药物，据报道，它通过部分阐明的机制发挥血管保护作用。本研究旨在评估 METF 对饮食诱导肥胖大鼠主动脉中 MAO 表达、ROS 产生和血管舒缩功能的影响。经过 24 周高热量垃圾食品（HCJF）饮食后，分离出主动脉环并进行 METF（10 μM，12 小时孵育）处理。使用定量 PCR 和免疫组织化学法测量 MAO 表达，使用光谱法和免疫荧光法测量 ROS 产生，使用肌动图研究测量血管反应性。从肥胖大鼠分离的主动脉环中 MAO 表达上调，同时 ROS 产生增加，血管反应性受损。METF 降低了 MAO 表达和 ROS 的产生，降低了血管收缩性，并改善了病变血管标本中的内皮依赖性舒张。总之，METF 通过减轻饮食诱导肥胖大鼠中 MAO 相关氧化应激发挥血管保护作用。
