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.
Keywords: Antioxidants; Atherosclerosis; Oxidative stress; Superoxide dismutase; Type 2 diabetes mellitus; Vascular calcification.
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