Exploration of the Crucial Genes and Molecular Mechanisms Mediating Atherosclerosis and Abnormal Endothelial Shear Stress. (12th August 2022)

• Record Type: Journal Article
• Authors: Zhu, Guoqi; Lai, Yan; Chen, Fei; Qian, Jun; Lin, Hao; Yuan, Deqiang; Yao, Tongqing; Liu, XueBo
• Other Names: Belluzzi Elisa Academic Editor.
• Is Part Of: Disease markers. Volume 2022(2022)
• Publication Date: 2022-08-12
• Subjects: Diagnosis -- Periodicals; Biochemical markers -- Periodicals; Pathology -- Periodicals; 616
• DOI: 10.1155/2022/6306845
• Languages: English
• ISSNs: 0278-0240

Abstract

Abstract : Background . Abnormal endothelial shear stress (ESS) is a significant risk factor for atherosclerosis (AS); however, the genes and pathways between ESS and AS are poorly understood. Here, we screened hub genes and potential regulatory targets linked to the progression of AS induced by abnormal ESS. Methods . The microarray data of ESS and AS were downloaded from the Gene Expression Omnibus (GEO) database. The coexpression modules related to shear stress and AS were identified with weighted gene coexpression network analysis (WGCNA). Coexpression genes in modules obtained from GSE28829 and GSE160611 were considered as SET1. The results were validated in validation set by differential gene analysis. The limma package in R was used to identify differentially expressed genes (DEGs). The common DEGs of GSE100927 and GSE103672 were regarded as SET2. Next, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted. Protein-protein interaction (PPI) enrichment analysis was assembled, and hub genes were identified using MCODE and ClueGO in Cytoscape. ROC curve analyses were conducted to assess the ability of common hub genes to distinguish samples of atherosclerotic plaque from normal arterial. The expression of common hub gene was verified in ox-LDL-induced foam cells and GSE41571. Results . We identified three gene modules (the blue, tan, and cyan modules) related to AS and three shear stress-related modules (the brown, red, and pink modules). A total of 129 genes in SET1 and 476 genes in SET2 were identified. CCRL2, LGALS9, and PLCB2 were identified as common hub genes and validated in the GSE100927, GSE28829, and GSE41571. ROC analysis indicates the expression of CCRL2, LGALS9, and PLCB2 could effectively distinguish the atherosclerotic plaque and normal arterial. The expression level of CCRL2, LGALS9, and PLCB2 increases with the accumulation of lipid increased. Conclusion . We identified CCRL2, LGALS9, and PLCB2 as key genes associated with abnormal ESS and AS and may provide potential prevention and treatment target of AS induced by abnormal ESS.