Andújar-Vera Francisco, García-Fontana Cristina, Sanabria-de la Torre Raquel, González-Salvatierra Sheila, Martínez-Heredia Luis, Iglesias-Baena Iván, Muñoz-Torres Manuel, García-Fontana Beatriz
Instituto de Investigación Biosanitaria de Granada, 18012 Granada, Spain.
Department of Computer Science and Artificial Intelligence, University of Granada, 18071 Granada, Spain.
Biomedicines. 2022 Feb 6;10(2):389. doi: 10.3390/biomedicines10020389.
The identification of common targets in Alzheimer's disease (AD) and cardiovascular disease (CVD) in recent years makes the study of the CVD/AD axis a research topic of great interest. Besides aging, other links between CVD and AD have been described, suggesting the existence of common molecular mechanisms. Our study aimed to identify common targets in the CVD/AD axis. For this purpose, genomic data from calcified and healthy femoral artery samples were used to identify differentially expressed genes (DEGs), which were used to generate a protein-protein interaction network, where a module related to AD was identified. This module was enriched with the functionally closest proteins and analyzed using different centrality algorithms to determine the main targets in the CVD/AD axis. Validation was performed by proteomic and data mining analyses. The proteins identified with an important role in both pathologies were apolipoprotein E and haptoglobin as DEGs, with a fold change about +2 and -2, in calcified femoral artery vs healthy artery, respectively, and clusterin and alpha-2-macroglobulin as close interactors that matched in our proteomic analysis. However, further studies are needed to elucidate the specific role of these proteins, and to evaluate its function as biomarkers or therapeutic targets.
近年来，阿尔茨海默病（AD）和心血管疾病（CVD）中共同靶点的发现使得CVD/AD轴的研究成为一个备受关注的研究课题。除了衰老之外，CVD和AD之间的其他联系也已被描述，这表明存在共同的分子机制。我们的研究旨在确定CVD/AD轴中的共同靶点。为此，利用钙化和健康股动脉样本的基因组数据来识别差异表达基因（DEG），这些基因被用于生成蛋白质-蛋白质相互作用网络，在该网络中识别出一个与AD相关的模块。该模块富含功能最接近的蛋白质，并使用不同的中心性算法进行分析，以确定CVD/AD轴中的主要靶点。通过蛋白质组学和数据挖掘分析进行验证。在两种疾病中起重要作用的蛋白质，作为DEG的载脂蛋白E和触珠蛋白，在钙化股动脉与健康动脉中，其倍数变化分别约为+2和-2，而在我们的蛋白质组学分析中，聚集素和α-2-巨球蛋白作为紧密相互作用蛋白与之匹配。然而，需要进一步研究来阐明这些蛋白质的具体作用，并评估其作为生物标志物或治疗靶点的功能。
