Identifying PTAFR as a hub gene in atherosclerosis: implications for NETosis and disease progression
Abstract Background Atherosclerosis (AS) is a major cause of cardiovascular diseases and neutrophil extracellular traps (NETs) may be actively involved in the development of atherosclerosis. Identifying key biomarkers in this process is essential for developing targeted treatments for AS. Methods We...
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BMC
2024-12-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-024-00708-3 |
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| author | Chaowen Ye Yunli Zhao Wei Yu Rongzhong Huang Tianyang Hu |
| author_facet | Chaowen Ye Yunli Zhao Wei Yu Rongzhong Huang Tianyang Hu |
| author_sort | Chaowen Ye |
| collection | DOAJ |
| description | Abstract Background Atherosclerosis (AS) is a major cause of cardiovascular diseases and neutrophil extracellular traps (NETs) may be actively involved in the development of atherosclerosis. Identifying key biomarkers in this process is essential for developing targeted treatments for AS. Methods We performed bioinformatics analysis using a NETosis-related gene (NRGs) set and three AS datasets (GSE100927, GSE21545, and GSE159677). Differential expression analysis and machine learning techniques (random forest and SVM-RFE) were used to screen for key NRGs. Functional enrichment analysis was conducted using GO and KEGG pathways. The expression and role of PTAFR and NETs in the mouse AS model were validated through histology, immunofluorescence, flow cytometry, and Western blot analysis. The regulatory relationship between PTAFR and NETs was confirmed by siRNA and antagonist intervention targeting PTAFR. Results We identified 24 differentially expressed NRGs in AS. Random Forest and SVM-RFE analyses highlighted PTAFR as a key gene. Prognostic analysis revealed PTAFR significantly impacts ischemic events in AS patients. WB and immunofluorescence confirmed increased levels of NETs and PTAFR in the mouse AS model. Single-cell analysis, flow cytometry, and immunofluorescence revealed that PTAFR is primarily distributed in macrophages and neutrophils. Cellular experiments further confirmed that PTAFR regulates NETs formation. Conclusion PTAFR is an important regulatory factor for NET formation in AS, influencing the progression and prognosis of atherosclerosis. Targeting PTAFR may provide new therapeutic strategies for AS. |
| format | Article |
| id | doaj-art-d264da2668544ec883d470d0beb5eeb9 |
| institution | OA Journals |
| issn | 1479-7364 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | Human Genomics |
| spelling | doaj-art-d264da2668544ec883d470d0beb5eeb92025-08-20T01:57:16ZengBMCHuman Genomics1479-73642024-12-0118111410.1186/s40246-024-00708-3Identifying PTAFR as a hub gene in atherosclerosis: implications for NETosis and disease progressionChaowen Ye0Yunli Zhao1Wei Yu2Rongzhong Huang3Tianyang Hu4Precision Medicine Center, The Second Affiliated Hospital of Chongqing Medical UniversityPrecision Medicine Center, The Second Affiliated Hospital of Chongqing Medical UniversityPrecision Medicine Center, The Second Affiliated Hospital of Chongqing Medical UniversityPrecision Medicine Center, The Second Affiliated Hospital of Chongqing Medical UniversityPrecision Medicine Center, The Second Affiliated Hospital of Chongqing Medical UniversityAbstract Background Atherosclerosis (AS) is a major cause of cardiovascular diseases and neutrophil extracellular traps (NETs) may be actively involved in the development of atherosclerosis. Identifying key biomarkers in this process is essential for developing targeted treatments for AS. Methods We performed bioinformatics analysis using a NETosis-related gene (NRGs) set and three AS datasets (GSE100927, GSE21545, and GSE159677). Differential expression analysis and machine learning techniques (random forest and SVM-RFE) were used to screen for key NRGs. Functional enrichment analysis was conducted using GO and KEGG pathways. The expression and role of PTAFR and NETs in the mouse AS model were validated through histology, immunofluorescence, flow cytometry, and Western blot analysis. The regulatory relationship between PTAFR and NETs was confirmed by siRNA and antagonist intervention targeting PTAFR. Results We identified 24 differentially expressed NRGs in AS. Random Forest and SVM-RFE analyses highlighted PTAFR as a key gene. Prognostic analysis revealed PTAFR significantly impacts ischemic events in AS patients. WB and immunofluorescence confirmed increased levels of NETs and PTAFR in the mouse AS model. Single-cell analysis, flow cytometry, and immunofluorescence revealed that PTAFR is primarily distributed in macrophages and neutrophils. Cellular experiments further confirmed that PTAFR regulates NETs formation. Conclusion PTAFR is an important regulatory factor for NET formation in AS, influencing the progression and prognosis of atherosclerosis. Targeting PTAFR may provide new therapeutic strategies for AS.https://doi.org/10.1186/s40246-024-00708-3AtherosclerosisNETosisNETsPTAFRCardiovascular diseases |
| spellingShingle | Chaowen Ye Yunli Zhao Wei Yu Rongzhong Huang Tianyang Hu Identifying PTAFR as a hub gene in atherosclerosis: implications for NETosis and disease progression Human Genomics Atherosclerosis NETosis NETs PTAFR Cardiovascular diseases |
| title | Identifying PTAFR as a hub gene in atherosclerosis: implications for NETosis and disease progression |
| title_full | Identifying PTAFR as a hub gene in atherosclerosis: implications for NETosis and disease progression |
| title_fullStr | Identifying PTAFR as a hub gene in atherosclerosis: implications for NETosis and disease progression |
| title_full_unstemmed | Identifying PTAFR as a hub gene in atherosclerosis: implications for NETosis and disease progression |
| title_short | Identifying PTAFR as a hub gene in atherosclerosis: implications for NETosis and disease progression |
| title_sort | identifying ptafr as a hub gene in atherosclerosis implications for netosis and disease progression |
| topic | Atherosclerosis NETosis NETs PTAFR Cardiovascular diseases |
| url | https://doi.org/10.1186/s40246-024-00708-3 |
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