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Mechanism Research of Platelet Core Marker Prediction and Molecular Recognition in Cardiovascular Events
Hongdan Wang1, Bingyu Zhang1, Xianhua Zhong1
1Chongqing Engineering Research Center of Medical Electronics and Information Technology, College of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.
Insights
This study identifies six core platelet biomarkers, including VEGFA, linked to cardiovascular and cerebrovascular diseases. Concanavalin A (ConA) shows potential as a therapeutic target by modulating VEGFA expression and platelet activation.
Area of Science:
- Biomedical research
- Bioinformatics
- Molecular biology
Background:
- Platelet activation is central to cardiovascular and cerebrovascular disease pathogenesis.
- Identifying reliable platelet biomarkers is crucial for disease management.
Purpose of the Study:
- To discover combined platelet biomarkers for cardiovascular diseases.
- To explore Concanavalin A (ConA) as a novel pharmacological target for platelet-related conditions.
Main Methods:
- Utilized high-throughput technology and bioinformatics analysis on gene expression profiles (GEO database).
- Identified differentially expressed genes (DEGs) using R language and performed enrichment analysis (GO, KEGG).
- Constructed protein-protein interaction (PPI) networks (STRING, Cytoscape) and docked ConA with core targets.
Main Results:
- Identified six core markers (CD34, SOCS2, ABL1, MTOR, VEGFA, SMURF1) common to acute myocardial infarction and sickle cell disease.
- VEGFA demonstrated the most significant interaction with ConA in molecular docking simulations.
Conclusions:
- VEGFA is a key target, likely downregulated by ConA, impacting the PI3K/Akt pathway in platelet activation.
- ConA interaction with core targets offers a potential therapeutic strategy for thrombosis and cardiovascular events.
Background:
Thrombosis triggered by platelet activation plays a vital role in the pathogenesis of cardiovascular and cerebrovascular diseases.
Objective:
This study aims to find platelet combined biomarkers for cardiovascular diseases and investigate the possibility of Concanavalin A (ConA) acting on platelets as a new pharmacological target.
Methods:
High-throughput Technology and bioinformatics analysis were combined and groups of microarray chip gene expression profiles for acute myocardial infarction (AMI) and sickle cell disease (SCD) were obtained using GEO database screening. R language limma package was used to obtain differentially expressed genes (DEGs). GO, KEGG, and other databases were utilized to perform the enrichment analysis of DEGs' functions, pathways, etc. PPI network was constructed using STRING database and Cytoscape software, and MCC algorithm was used to obtain the 200 core genes of the two groups of DEGs. Core targets were confirmed by constructing an intersection area screening. A type of molecular probe, ConA, was molecularly docked with the above core targets on the Zdock, HEX, and 3D-DOCK servers.
Results:
We found six core markers, CD34, SOCS2, ABL1, MTOR, VEGFA, and SMURF1, which were simultaneously related to both diseases, and the docking effect showed that VEGFA is the best-performing.
Conclusion:
VEGFA is most likely to reduce its expression by binding to ConA, which could affect the downstream regulation of the PI3K/Akt signaling pathway during platelet activation. Some other core targets also have the opportunity to interact with ConA to affect platelet-activated thrombosis and trigger changes in cardiovascular events.
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