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. 2021 Feb;9(3):267.
doi: 10.21037/atm-21-193.

Identification of key pathways and core genes involved in atherosclerotic plaque progression

Rong Yang  1 , Linpeng Yao  1 , Chengli Du  2 , Yihe Wu  2
Affiliations

Identification of key pathways and core genes involved in atherosclerotic plaque progression

Rong Yang et al. Ann Transl Med. 2021 Feb.

Abstract

Background: Atherosclerosis leads to the occurrence of cardiovascular diseases. However, the molecular mechanisms that contribute to atherosclerotic plaque rupture are incompletely characterized. We aimed to identify the genes related to atherosclerotic plaque progression that could serve as novel biomarkers and interventional targets for plaque progression.

Methods: The datasets of GSE28829 in early vs. advanced atherosclerotic plaques and those of GSE41571 in stable vs. ruptured plaques from Gene Expression Omnibus (GEO) were analyzed by using bioinformatics methods. In addition, we used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the expression level of core genes in a mouse atherosclerosis model.

Results: There were 29 common differentially expressed genes (DEGs) between the GSE28829 and GSE41571 datasets, and the DEGs were mainly enriched in the chemokine signaling pathway and the Staphylococcus aureus infection pathway (P<0.05). We identified 6 core genes (FPR3, CCL18, MS4A4A, CXCR4, CXCL2, and C1QB) in the protein-protein interaction (PPI) network, 3 of which (CXCR4, CXCL2, and CCL18) were markedly enriched in the chemokine signaling pathway. qRT-PCR analysis showed that the messenger RNA levels of two core genes (CXCR4 and CXCL2) increased significantly during plaque progression in the mouse atherosclerosis model.

Conclusions: In summary, bioinformatics techniques proved useful for the screening and identification of novel biomarkers of disease. A total of 29 DEGs and 6 core genes were linked to atherosclerotic plaque progression, in particular the CXCR4 and CXCL2 genes.

Keywords: Atherosclerosis; bioinformatics; core genes; differentially expressed genes (DEGs); molecular mechanism.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-193). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
A total of 29 common DEGs in the two datasets (GSE28829 and GSE41571) were identified through Venn diagram software. (A) A total of 29 DEGs were upregulated (log FC >0), and (B) 0 DEGs were downregulated (log FC <0). DEGs, differentially expressed genes.
Figure 2
Figure 2
Four genes (RAC2, CXCR4, CXCL2, and CCL18) were significantly enriched in the chemokine signaling pathway. RAC means RAC2; Chemokine means CXCL2 and CCL18; Chemokine R means CXCR4.
Figure 3
Figure 3
The PPI network of common DEGs was constructed by the STRING online database and module analysis. (A) A total of 18 DEGs were included in the DEG PPI network; (B) core genes in the PPI network. PPI, protein-protein interaction; DEGs, differentially expressed genes.
Figure 4
Figure 4
Corroboration of two core genes using qRT-PCR. (A) Oil Red O-stained mice aortas; (B) Relative expression of the CXCR4 measured by qRT-PCR; (C) Relative expression of the CXCL2 measured by qRT-PCR. qRT-PCR, quantitative reverse transcription quantitative polymerase chain reaction.
See this image and copyright information in PMC

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