Related Experiment Video
Updated: Oct 6, 2025
Isolation and Identification of Vascular Endothelial Cells from Distinct Adipose Depots for Downstream Applications
Published on: June 10, 2022
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.
Insights
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.
Abstract:
Atherosclerosis is the most notable cardiovascular disease, the latter being the main cause of death globally. Endothelial cell dysfunction plays a major role in the pathogenesis of atherosclerosis. However, it is currently unclear which genes are involved between endothelial cell dysfunction and atherosclerosis. This study was aimed at identifying these genes. Based on the GSE83500 dataset, the quantification of endothelial cell function was conducted using single-sample gene set enrichment analysis; the coexpression modules were conducted using weighted correlation network analysis. After building module-trait relationships, tan and yellow modules were regarded as hub modules. 10 hub genes from each hub module were identified by the protein-protein interaction network analysis. The key genes (RAB5A, CTTN, ITGB1, and MMP9) were obtained by comparing the expression differences of the hub gene between atherosclerotic and normal groups from the GSE28829 and GSE43292 datasets, respectively. ROC analysis showed the diagnostic value of key genes. Moreover, the differential expression of key genes in normal and atherosclerotic aortic walls was verified. In vitro, we establish a model of ox-LDL-injured endothelial cells and transfect RAB5A overexpression and shRNA plasmids. The results showed that overexpression of RAB5A ameliorates the proliferation and migration function of ox-LDL-injured endothelial cells, including the ability of tubule formation. It was speculated that the interferon response, Notch signaling pathways, etc. were involved in this function of RAB5A by using gene set variation analysis. With the multiple bioinformatics analysis methods, we detected that yellow and tan modules are related to the abnormal proliferation and migration of endothelial cells associated with atherosclerosis. RAB5A, CTTN, ITGB1, and MMP9 can be used as potential targets for therapy and diagnostic markers. In vitro, overexpression of RAB5A can ameliorate the proliferation and migration function of ox-LDL-injured endothelial cells, and the possible molecules involved in this process were speculated.
