Department VI-Cardiology, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, E. Murgu Sq. no 2, 300041 Timișoara, Romania.
Research Centre of the Institute of Cardiovascular Diseases, G. Adam Str. no 13A, 300310 Timișoara, Romania.
Int J Mol Sci. 2024 Sep 25;25(19):10307. doi: 10.3390/ijms251910307.
Monoamine oxidases (MAOs), mitochondrial enzymes that constantly produce hydrogen peroxide (HO) as a byproduct of their activity, have been recently acknowledged as contributors to oxidative stress in cardiometabolic pathologies. The present study aimed to assess whether MAOs are mediators of valvular oxidative stress and interact in vitro with angiotensin 2 (ANG2) to mimic the activation of the renin-angiotensin system. To this aim, valvular tissue samples were harvested from 30 patients diagnosed with severe primary mitral regurgitation and indication for surgical repair. Their reactive oxygen species (ROS) levels were assessed by means of a ferrous oxidation xylenol orange (FOX) assay, while MAO expression was assessed by immune fluorescence (protein) and qRT-PCR (mRNA). The experiments were performed using native valvular tissue acutely incubated or not with angiotensin 2 (ANG2), MAO inhibitors (MAOI) and the angiotensin receptor blocker, irbesartan (Irb). Correlations between oxidative stress and echocardiographic parameters were also analyzed. Ex vivo incubation with ANG2 increased MAO-A and -B expression and ROS generation. The level of valvular oxidative stress was negatively correlated with the left ventricular ejection fraction. MAOI and Irb reduced valvular HO production. In conclusion, both MAO isoforms are expressed in pathological human mitral valves and contribute to local oxidative stress and ventricular functional impairment and can be modulated by the local renin-angiotensin system
单胺氧化酶（MAO）是线粒体酶，其活性的副产物不断产生过氧化氢（HO），最近被认为是心脏代谢病理中氧化应激的贡献者。本研究旨在评估 MAO 是否是瓣膜氧化应激的介质，并在体外与血管紧张素 2（ANG2）相互作用以模拟肾素-血管紧张素系统的激活。为此，从 30 名被诊断为严重原发性二尖瓣反流并需要手术修复的患者中采集瓣膜组织样本。通过亚铁氧化邻甲氨基酚（FOX）测定法评估其活性氧（ROS）水平，通过免疫荧光（蛋白质）和 qRT-PCR（mRNA）评估 MAO 表达。使用天然瓣膜组织进行急性孵育或不孵育血管紧张素 2（ANG2）、MAO 抑制剂（MAOI）和血管紧张素受体阻滞剂厄贝沙坦（Irb）进行实验。还分析了氧化应激与超声心动图参数之间的相关性。体外孵育 ANG2 增加了 MAO-A 和 -B 的表达和 ROS 的产生。瓣膜氧化应激水平与左心室射血分数呈负相关。MAOI 和 Irb 减少了瓣膜 HO 的产生。总之，两种 MAO 同工酶都在病理性人二尖瓣中表达，并导致局部氧化应激和心室功能障碍，并且可以通过局部肾素-血管紧张素系统进行调节。
