Dataset related to the article "Impact of Oxidative Stress and Protein S-Glutathionylation in Aortic Valve Sclerosis Patients with Overt Atherosclerosis"

This record contains raw data related to the article "Impact of Oxidative Stress and Protein S-Glutathionylation in Aortic Valve Sclerosis Patients with Overt Atherosclerosis" <strong>Abstract</strong> Aortic valve sclerosis (AVSc) is characterized by non-uniform thickening of the leaflets without hemodynamic changes. Endothelial dysfunction, also caused by dysregulation of glutathione homeostasis expressed as ratio between its reduced (GSH) and its oxidised form (GSSG), could represent one of the pathogenic triggers of AVSc. We prospectively enrolled 58 patients with overt atherosclerosis and requiring coronary artery bypass grafting (CABG). The incidence of AVSc in the studied population was 50%. The two groups (No-AVSc and AVSc) had similar clinical characteristics. Pre-operatively, AVSc group showed significantly lower GSH/GSSG ratio than No-AVSc group (<em>p = </em>0.02). Asymmetric dimethylarginine (ADMA) concentration was significantly higher in AVSc patients compared to No-AVSc patients (<em>p &lt; </em>0.0001). Explanted sclerotic aortic valves presented a significantly increased protein glutathionylation (Pr-SSG) than No-AVSc ones (<em>p = </em>0.01). In vitro, inhibition of glutathione reductase caused β-actin glutathionylation, activation of histone 2AX, upregulation of α2 smooth muscle actin (<em>ACTA2</em>), downregulation of platelet and endothelial cell adhesion molecule 1 (<em>PECAM1</em>) and cadherin 5 (<em>CDH5</em>). In this study, we showed for the first time that the dysregulation of glutathione homeostasis is associated with AVSc. We found that Pr-SSG is increased in AVSc leaflets and it could lead to EndMT via DNA damage. Further studies are warranted to elucidate the causal role of Pr-SSG in aortic valve degeneration.本数据集包含与论文《显性动脉粥样硬化患者氧化应激与蛋白质S-谷胱甘肽化在主动脉瓣硬化中的作用》相关的原始数据。 **摘要** 主动脉瓣硬化（aortic valve sclerosis, AVSc）以瓣膜叶非均匀增厚且无血流动力学改变为特征。内皮功能障碍可由谷胱甘肽（glutathione）稳态失调引发，该失调表现为还原型谷胱甘肽（reduced glutathione, GSH）与氧化型谷胱甘肽（oxidised form, GSSG）的比值异常，其可能是主动脉瓣硬化的致病触发因素之一。本研究前瞻性纳入58例确诊动脉粥样硬化且需接受冠状动脉旁路移植术（coronary artery bypass grafting, CABG）的患者。受试人群中主动脉瓣硬化的发生率为50%。无主动脉瓣硬化组（No-AVSc）与主动脉瓣硬化组（AVSc）的临床基线特征相似。术前检测显示，主动脉瓣硬化组的GSH/GSSG比值显著低于无主动脉瓣硬化组（*p* = 0.02）。主动脉瓣硬化患者的不对称二甲基精氨酸（asymmetric dimethylarginine, ADMA）浓度显著高于无主动脉瓣硬化组患者（*p* < 0.0001）。相较于无主动脉瓣硬化的瓣膜，切除的硬化主动脉瓣的蛋白质S-谷胱甘肽化（protein S-glutathionylation, Pr-SSG）水平显著升高（*p* = 0.01）。体外实验中，抑制谷胱甘肽还原酶可引发β-肌动蛋白（β-actin）S-谷胱甘肽化、组蛋白H2AX（histone 2AX）激活、α2平滑肌肌动蛋白（α2 smooth muscle actin, ACTA2）表达上调、血小板与内皮细胞黏附分子1（platelet and endothelial cell adhesion molecule 1, PECAM1）及钙黏蛋白5（cadherin 5, CDH5）表达下调。本研究首次证实谷胱甘肽稳态失调与主动脉瓣硬化相关。我们发现主动脉瓣硬化瓣膜叶内的蛋白质S-谷胱甘肽化水平升高，其可能通过DNA损伤介导内皮间质转化（endothelial-mesenchymal transition, EndMT）。未来需开展进一步研究以阐明蛋白质S-谷胱甘肽化在主动脉瓣退行性病变中的因果作用。