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Updated: Jun 21, 2025
A Methodological Approach to Non-invasive Assessments of Vascular Function and Morphology
Published on: February 7, 2015
Identification of key biomarkers of endothelial dysfunction in hypertension with carotid atherosclerosis based on
Yimin Wang1, Xinyang Shou2, Yuteng Wu2
1The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310005, China.
Insights
Two key genes, CCR1 and NCKAP1L, involved in immune responses, were identified as crucial in carotid atherosclerosis (CAS) development and endothelial dysfunction in hypertensive patients.
Area of Science:
- Cardiovascular Biology
- Genomics
- Immunology
Background:
- Endothelial dysfunction precedes carotid atherosclerosis (CAS) in hypertensive patients.
- Identifying hub genes is crucial for understanding CAS pathogenesis.
- This study focuses on uncovering key genes in endothelial dysfunction related to CAS.
Purpose of the Study:
- To identify hub genes associated with endothelial dysfunction in carotid atherosclerosis (CAS).
- To elucidate the pathological mechanisms underlying CAS progression in hypertension.
- To validate potential therapeutic targets for CAS.
Main Methods:
- Gene expression profiles from GSE43292 dataset were analyzed.
- Weighted gene correlation network analysis (WGCNA) and LASSO regression identified hub genes.
- Gene Ontology (GO) and KEGG pathway analyses explored biological functions.
- In vitro experiments validated hub gene expression in human umbilical vein endothelial cells (HUVECs).
Main Results:
- 161 differentially expressed genes were identified in CAS plaques.
- The gray60 module from WGCNA was significantly associated with clinical features.
- Immune response pathways were highlighted by GO and KEGG analyses.
- Two hub genes, CCR1 and NCKAP1L, were identified via LASSO regression.
- mRNA expression of CCR1 and NCKAP1L increased in ox-LDL treated HUVECs.
Conclusions:
- Hub genes related to immune responses play a role in CAS development.
- CCR1 and NCKAP1L are identified as key hub genes in endothelial dysfunction.
- These genes represent potential therapeutic targets for CAS in hypertensive patients.
Background:
Endothelial dysfunction is the early stage of carotid atherosclerosis (CAS) in patients with hypertension. It is worth identifying the potential hub genes of endothelial dysfunction to elucidate pathological mechanism in the progression of the disease.
Method:
We obtained gene expression profiles of GSE43292 from the Gene Expression Omnibus (GEO) database. Hub genes associated with CAS were identified through weighted gene correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore potential biological mechanisms and signaling pathways. Finally, in vitro experiments on human umbilical vein endothelial cells (HUVECs) were conducted to validate these hub genes.
Results:
The microarray dataset GSE43292 included 32 CAS plaques samples and corresponding macroscopically intact tissues from patients with hypertension. A total of 161 differentially expressed genes were discovered. Through WGCNA analysis, the gray60 module emerged as the most significant module associated with clinical features. The GO and KEGG enrichment analyses of genes in the gray60 module highlighted the substantial involvement of immune response-related signaling pathways. Two key hub genes (CCR1 and NCKAP1L) were pinpointed via LASSO regression. We found a significant increase in the mRNA expression level of the hub genes in oxidized low density lipoprotein (ox-LDL) treated HUVECs.
Conclusions:
Our study indicated that the hub genes related to immune responses are involved in the development of CAS. Two hub genes (CCR1 and NCKAP1L) of endothelial dysfunction were identified. These genes may provide a valuable therapeutic target of CAS in patients with hypertension.
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