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Identification of Potential Targets Linked to the Cardiovascular/Alzheimer's Axis through Bioinformatics Approaches
Francisco Andújar-Vera1,2,3, Cristina García-Fontana1,4,5, Raquel Sanabria-de la Torre1,6
1Instituto de Investigación Biosanitaria de Granada, 18012 Granada, Spain.
Abstract:
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.
Insights
Researchers identified key proteins linking cardiovascular disease (CVD) and Alzheimer's disease (AD). Apolipoprotein E and haptoglobin were significant differentially expressed genes, offering potential therapeutic targets for both conditions.
Area of Science:
- Biomedical research
- Genomics
- Proteomics
Background:
- Alzheimer's disease (AD) and cardiovascular disease (CVD) share common molecular mechanisms beyond aging.
- Investigating the CVD/AD axis is crucial for understanding shared pathologies.
Purpose of the Study:
- To identify common molecular targets in the CVD/AD axis.
- To pinpoint key proteins involved in both cardiovascular and neurodegenerative diseases.
Main Methods:
- Analysis of genomic data from calcified and healthy femoral artery samples.
- Construction of a protein-protein interaction network to identify differentially expressed genes (DEGs).
- Application of centrality algorithms and proteomic analysis for target validation.
Main Results:
- Apolipoprotein E and haptoglobin identified as DEGs in calcified arteries, suggesting roles in CVD/AD.
- Clusterin and alpha-2-macroglobulin identified as significant interacting proteins.
- The study highlights shared molecular pathways between cardiovascular and Alzheimer's diseases.
Conclusions:
- Apolipoprotein E, haptoglobin, clusterin, and alpha-2-macroglobulin are potential key targets in the CVD/AD axis.
- These proteins may serve as future biomarkers or therapeutic targets for AD and CVD.
- Further research is necessary to fully elucidate the roles of these identified proteins.
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