Instituto De Investigación Biosanitaria de Granada (Ibs.GRANADA), Granada, Spain; Fundación para la Investigación Biosanitaria de Andalucía Oriental (FIBAO), Avda. de Madrid 15, 18012 Granada, Spain.
Instituto De Investigación Biosanitaria de Granada (Ibs.GRANADA), Granada, Spain; Angiology and Vascular Surgery Unit, Universitary San Cecilio Hospital, Avda. del conocimiento s/n, 18016 Granada, Spain.
J Pharm Biomed Anal. 2020 Oct 25;190:113535. doi: 10.1016/j.jpba.2020.113535. Epub 2020 Aug 13.
Currently, there are not many in-depth studies focusing on the protein analysis of antioxidants involved in the calcification of the femoral artery. In this context, this study aimed to increase the knowledge of the molecular redox mechanisms involved in this process. Samples from calcified femoral artery sections of seven patients diagnosed with type 2 diabetes (T2D) and critical ischemia were analyzed. The isolated proteins were identified using liquid chromatography and mass-mass spectrometry and were used to generate a protein-protein interaction (PPI) network. Subsequently, highly interconnected regions within the PPI network were identified to obtain a representative module linked to oxidative stress. The proteins of this module with a higher degree of centrality (hubs) were selected to validate them by datamining, transcriptomic and proteomic assays. The analysis of modules of the femoral PPI network showed a module with mainly antioxidant function in which superoxide dismutase 2 (SOD2) was reported as the most important hub. SOD2 was validated at transcriptomic and proteomic level and confirmed by datamining. These results indicate that SOD activity is highly linked to the atherosclerotic process. We suggest that SOD2 could be a potential therapeutic target to prevent the calcification of the femoral artery. The maintenance of optimal SOD2 levels and its cofactors could be used as a preventive strategy for vascular calcification and the related cardiovascular complications in T2D patients.
目前，针对参与股动脉钙化的抗氧化剂的蛋白质分析，还没有太多深入的研究。在这种情况下，本研究旨在增加对该过程中涉及的分子氧化还原机制的了解。分析了 7 名被诊断患有 2 型糖尿病（T2D）和严重缺血的患者的钙化股动脉切片中的样本。使用液相色谱和质谱联用技术对分离出的蛋白质进行鉴定，并用于生成蛋白质-蛋白质相互作用（PPI）网络。随后，鉴定 PPI 网络中高度相互连接的区域，以获得与氧化应激相关的代表性模块。选择该模块中具有较高中心度（枢纽）的蛋白质，通过数据挖掘、转录组学和蛋白质组学检测进行验证。对股 PPI 网络模块的分析显示，该模块主要具有抗氧化功能，其中超氧化物歧化酶 2（SOD2）被报告为最重要的枢纽。在转录组学和蛋白质组学水平上对 SOD2 进行了验证，并通过数据挖掘得到了确认。这些结果表明 SOD 活性与动脉粥样硬化过程密切相关。我们建议 SOD2 可能是预防股动脉钙化的潜在治疗靶点。维持最佳 SOD2 水平及其辅助因子可作为预防 T2D 患者血管钙化及相关心血管并发症的策略。
