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Identification of core genes associated with the anti-atherosclerotic effects of Salvianolic acid B and immune cell infiltration characteristics using bioinformatics analysis
BACKGROUND: Atherosclerosis (AS) is the greatest contributor to pathogenesis of atherosclerotic cardiovascular disease (ASCVD), which is associated with increased mortality and reduced quality of life. Early intervention to mitigate AS is key to prevention of ASCVD. Salvianolic acid B (Sal B) is mai...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288713/ https://www.ncbi.nlm.nih.gov/pubmed/35842645 http://dx.doi.org/10.1186/s12906-022-03670-6 |
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author | Jin, Zheng Zhao, Huanyi Luo, Yuan Li, Xiushen Cui, Jiayan Yan, Jing Yang, Pingzhen |
author_facet | Jin, Zheng Zhao, Huanyi Luo, Yuan Li, Xiushen Cui, Jiayan Yan, Jing Yang, Pingzhen |
author_sort | Jin, Zheng |
collection | PubMed |
description | BACKGROUND: Atherosclerosis (AS) is the greatest contributor to pathogenesis of atherosclerotic cardiovascular disease (ASCVD), which is associated with increased mortality and reduced quality of life. Early intervention to mitigate AS is key to prevention of ASCVD. Salvianolic acid B (Sal B) is mainly extracted from root and rhizome of Salvia Miltiorrhiza Bunge, and exerts anti-atherosclerotic effect. The purpose of this study was to screen for anti-AS targets of Sal B and to characterize immune cell infiltration in AS. METHODS: We identified targets of Sal B using SEA (http://sea.bkslab.org/) and SIB (https://www.sib.swiss/) databases. GSE28829 and GSE43292 datasets were obtained from Gene Expression Omnibus database. We identified differentially expressed genes (DEGs) and performed enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was used to determine the most relevant module associated with atherosclerotic plaque stability. Intersecting candidate genes were evaluated by generating receiver operating characteristic (ROC) curves and molecular docking. Then, immune cell types were identified using CIBERSOFT and single-sample gene set enrichment analysis (ssGSEA), the relationship between candidate genes and immune cell infiltration was evaluated. Finally, a network-based approach to explore the candidate genes relationship with microRNAs (miRNAs) and Transcription factors (TFs). RESULTS: MMP9 and MMP12 were been selected as candidate genes from 64 Sal B-related genes, 81 DEGs and turquoise module with 220 genes. ROC curve results showed that MMP9 (AUC = 0.815, P<0.001) and MMP12 (AUC = 0.763, P<0.001) were positively associated with advanced atherosclerotic plaques. The results of immune infiltration showed that B cells naive, B cells memory, Plasma cells, T cells CD8, T cells CD4 memory resting, T cells CD4 memory activated, T cells regulatory (Tregs), T cells gamma delta, NK cells activated, Monocytes, and Macrophages M0 may be involved in development of AS, and the candidate genes MMP9 and MMP12 were associated with these immune cells to different degrees. What’ s more, miR-34a-5p and FOXC1, JUN maybe the most important miRNA and TFs. CONCLUSION: The anti-AS effects of Sal B may be related to MMP9 and MMP12 and associated with immune cell infiltration, which is expected to be used in the early intervention of AS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-022-03670-6. |
format | Online Article Text |
id | pubmed-9288713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-92887132022-07-18 Identification of core genes associated with the anti-atherosclerotic effects of Salvianolic acid B and immune cell infiltration characteristics using bioinformatics analysis Jin, Zheng Zhao, Huanyi Luo, Yuan Li, Xiushen Cui, Jiayan Yan, Jing Yang, Pingzhen BMC Complement Med Ther Research BACKGROUND: Atherosclerosis (AS) is the greatest contributor to pathogenesis of atherosclerotic cardiovascular disease (ASCVD), which is associated with increased mortality and reduced quality of life. Early intervention to mitigate AS is key to prevention of ASCVD. Salvianolic acid B (Sal B) is mainly extracted from root and rhizome of Salvia Miltiorrhiza Bunge, and exerts anti-atherosclerotic effect. The purpose of this study was to screen for anti-AS targets of Sal B and to characterize immune cell infiltration in AS. METHODS: We identified targets of Sal B using SEA (http://sea.bkslab.org/) and SIB (https://www.sib.swiss/) databases. GSE28829 and GSE43292 datasets were obtained from Gene Expression Omnibus database. We identified differentially expressed genes (DEGs) and performed enrichment analysis. Weighted gene co-expression network analysis (WGCNA) was used to determine the most relevant module associated with atherosclerotic plaque stability. Intersecting candidate genes were evaluated by generating receiver operating characteristic (ROC) curves and molecular docking. Then, immune cell types were identified using CIBERSOFT and single-sample gene set enrichment analysis (ssGSEA), the relationship between candidate genes and immune cell infiltration was evaluated. Finally, a network-based approach to explore the candidate genes relationship with microRNAs (miRNAs) and Transcription factors (TFs). RESULTS: MMP9 and MMP12 were been selected as candidate genes from 64 Sal B-related genes, 81 DEGs and turquoise module with 220 genes. ROC curve results showed that MMP9 (AUC = 0.815, P<0.001) and MMP12 (AUC = 0.763, P<0.001) were positively associated with advanced atherosclerotic plaques. The results of immune infiltration showed that B cells naive, B cells memory, Plasma cells, T cells CD8, T cells CD4 memory resting, T cells CD4 memory activated, T cells regulatory (Tregs), T cells gamma delta, NK cells activated, Monocytes, and Macrophages M0 may be involved in development of AS, and the candidate genes MMP9 and MMP12 were associated with these immune cells to different degrees. What’ s more, miR-34a-5p and FOXC1, JUN maybe the most important miRNA and TFs. CONCLUSION: The anti-AS effects of Sal B may be related to MMP9 and MMP12 and associated with immune cell infiltration, which is expected to be used in the early intervention of AS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-022-03670-6. BioMed Central 2022-07-16 /pmc/articles/PMC9288713/ /pubmed/35842645 http://dx.doi.org/10.1186/s12906-022-03670-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Jin, Zheng Zhao, Huanyi Luo, Yuan Li, Xiushen Cui, Jiayan Yan, Jing Yang, Pingzhen Identification of core genes associated with the anti-atherosclerotic effects of Salvianolic acid B and immune cell infiltration characteristics using bioinformatics analysis |
title | Identification of core genes associated with the anti-atherosclerotic effects of Salvianolic acid B and immune cell infiltration characteristics using bioinformatics analysis |
title_full | Identification of core genes associated with the anti-atherosclerotic effects of Salvianolic acid B and immune cell infiltration characteristics using bioinformatics analysis |
title_fullStr | Identification of core genes associated with the anti-atherosclerotic effects of Salvianolic acid B and immune cell infiltration characteristics using bioinformatics analysis |
title_full_unstemmed | Identification of core genes associated with the anti-atherosclerotic effects of Salvianolic acid B and immune cell infiltration characteristics using bioinformatics analysis |
title_short | Identification of core genes associated with the anti-atherosclerotic effects of Salvianolic acid B and immune cell infiltration characteristics using bioinformatics analysis |
title_sort | identification of core genes associated with the anti-atherosclerotic effects of salvianolic acid b and immune cell infiltration characteristics using bioinformatics analysis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288713/ https://www.ncbi.nlm.nih.gov/pubmed/35842645 http://dx.doi.org/10.1186/s12906-022-03670-6 |
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