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Identification of Key Genes Associated with Endothelial Cell Dysfunction in Atherosclerosis Using Multiple
Guofu Zhang1,2,3, Hui Yu1,3, Jingjing Su1
1Department of Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Biomed Research International
|January 21, 2022
Summary
Researchers identified key genes, including RAB5A, CTTN, ITGB1, and MMP9, involved in endothelial cell dysfunction and atherosclerosis. Overexpression of RAB5A improved endothelial cell function in vitro, suggesting potential therapeutic targets for cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Bioinformatics
Background:
- Atherosclerosis, a leading global cause of death, is strongly linked to endothelial cell dysfunction.
- The specific genes mediating the connection between endothelial dysfunction and atherosclerosis remain largely unidentified.
- Understanding these genetic links is crucial for developing novel therapeutic and diagnostic strategies.
Purpose of the Study:
- To identify key genes involved in endothelial cell dysfunction contributing to atherosclerosis.
- To evaluate the diagnostic potential of identified genes in atherosclerosis.
- To investigate the functional role of identified genes, particularly RAB5A, in endothelial cells.
Main Methods:
- Utilized gene expression datasets (GSE83500, GSE28829, GSE43292) for analysis.
- Employed single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA).
- Integrated protein-protein interaction (PPI) networks, differential expression analysis, ROC analysis, and in vitro cell models (ox-LDL injured endothelial cells).
Main Results:
- Identified 'tan' and 'yellow' coexpression modules significantly associated with endothelial cell dysfunction in atherosclerosis.
- Pinpointed four key genes (RAB5A, CTTN, ITGB1, MMP9) with diagnostic value for atherosclerosis.
- Demonstrated that RAB5A overexpression ameliorates proliferation, migration, and tubule formation in ox-LDL-injured endothelial cells, suggesting involvement of interferon response and Notch signaling.
Conclusions:
- RAB5A, CTTN, ITGB1, and MMP9 are identified as potential diagnostic markers and therapeutic targets for atherosclerosis.
- RAB5A plays a protective role in endothelial cells against ox-LDL-induced injury, impacting cellular functions.
- The study provides novel insights into the genetic underpinnings of endothelial dysfunction in atherosclerosis.
