Identification of pyroptosis related genes and subtypes in atherosclerosis using multiomic and single cell analysis
Abstract Atherosclerosis (AS), the leading cause of cardiovascular diseases, is a chronic inflammatory disorder involving lipid metabolism, immune dysregulation, and cell death. Pyroptosis, a form of inflammatory programmed cell death, is implicated in AS progression, yet its molecular mechanisms an...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-04398-2 |
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| author | Kaisheng Jiang Yang He Bingjie Hu Li Quan Longyun Peng Juntao Tian Nan Zhou Erwen Huang Qianhao Zhao |
| author_facet | Kaisheng Jiang Yang He Bingjie Hu Li Quan Longyun Peng Juntao Tian Nan Zhou Erwen Huang Qianhao Zhao |
| author_sort | Kaisheng Jiang |
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| description | Abstract Atherosclerosis (AS), the leading cause of cardiovascular diseases, is a chronic inflammatory disorder involving lipid metabolism, immune dysregulation, and cell death. Pyroptosis, a form of inflammatory programmed cell death, is implicated in AS progression, yet its molecular mechanisms and therapeutic potential remain incompletely understood. A multi-omics framework integrating transcriptomics, single-cell RNA sequencing, and machine learning to identify and prioritize pyroptosis-related genes (PRGs) in AS. Functional enrichment, immune infiltration profiling, and protein–protein interaction network analyses were conducted. Experimental validation was conducted using in vitro and in vivo models. Thirty-six PRGs were identified, with TREM2, TNF, MMP9, IL1B, and CASP1 emerging as key regulators of pyroptosis and inflammation. These PRGs demonstrated robust diagnostic potential in internal and external datasets. Immune infiltration analysis stratified AS patients into subtypes, with Cluster 2 characterized by elevated macrophage pyroptosis and a pro-inflammatory immune microenvironment. Single-cell analysis confirmed TREM2 upregulation in macrophages and monocytes, linking it to immune activation and plaque instability. Experimental validation revealed TREM2’s dual role in promoting macrophage lipid accumulation and pyroptosis. This study establishes PRGs, particularly TREM2, as critical modulators of AS progression. These findings enhance our understanding of pyroptosis in AS and provide a framework for developing PRG-based diagnostic and therapeutic strategies. |
| format | Article |
| id | doaj-art-6f6fce99e6864acf9aabd3990e81a42f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-6f6fce99e6864acf9aabd3990e81a42f2025-08-20T04:01:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-04398-2Identification of pyroptosis related genes and subtypes in atherosclerosis using multiomic and single cell analysisKaisheng Jiang0Yang He1Bingjie Hu2Li Quan3Longyun Peng4Juntao Tian5Nan Zhou6Erwen Huang7Qianhao Zhao8Faculty of Forensic Medicine, Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Zhongshan School of Medicine, Sun Yat-Sen UniversityFaculty of Forensic Medicine, Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Zhongshan School of Medicine, Sun Yat-Sen UniversityDivision of Forensic Medicine, Department of Pathology, School of Basic Medical Sciences, Guangzhou Medical UniversityFaculty of Forensic Medicine, Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Cardiology, The First Affiliated Hospital, Sun Yat-Sen UniversityZhongshan School of Medicine, Sun Yat-Sen UniversityPublic Order Administration Detachment, Changsha Municipal Public Security BureauFaculty of Forensic Medicine, Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Zhongshan School of Medicine, Sun Yat-Sen UniversityDepartment of Human Anatomy, School of Basic Medical Sciences, Guangzhou University of Chinese MedicineAbstract Atherosclerosis (AS), the leading cause of cardiovascular diseases, is a chronic inflammatory disorder involving lipid metabolism, immune dysregulation, and cell death. Pyroptosis, a form of inflammatory programmed cell death, is implicated in AS progression, yet its molecular mechanisms and therapeutic potential remain incompletely understood. A multi-omics framework integrating transcriptomics, single-cell RNA sequencing, and machine learning to identify and prioritize pyroptosis-related genes (PRGs) in AS. Functional enrichment, immune infiltration profiling, and protein–protein interaction network analyses were conducted. Experimental validation was conducted using in vitro and in vivo models. Thirty-six PRGs were identified, with TREM2, TNF, MMP9, IL1B, and CASP1 emerging as key regulators of pyroptosis and inflammation. These PRGs demonstrated robust diagnostic potential in internal and external datasets. Immune infiltration analysis stratified AS patients into subtypes, with Cluster 2 characterized by elevated macrophage pyroptosis and a pro-inflammatory immune microenvironment. Single-cell analysis confirmed TREM2 upregulation in macrophages and monocytes, linking it to immune activation and plaque instability. Experimental validation revealed TREM2’s dual role in promoting macrophage lipid accumulation and pyroptosis. This study establishes PRGs, particularly TREM2, as critical modulators of AS progression. These findings enhance our understanding of pyroptosis in AS and provide a framework for developing PRG-based diagnostic and therapeutic strategies.https://doi.org/10.1038/s41598-025-04398-2AtherosclerosisPyroptosisTREM2Multi-omics analysisImmune microenvironment |
| spellingShingle | Kaisheng Jiang Yang He Bingjie Hu Li Quan Longyun Peng Juntao Tian Nan Zhou Erwen Huang Qianhao Zhao Identification of pyroptosis related genes and subtypes in atherosclerosis using multiomic and single cell analysis Scientific Reports Atherosclerosis Pyroptosis TREM2 Multi-omics analysis Immune microenvironment |
| title | Identification of pyroptosis related genes and subtypes in atherosclerosis using multiomic and single cell analysis |
| title_full | Identification of pyroptosis related genes and subtypes in atherosclerosis using multiomic and single cell analysis |
| title_fullStr | Identification of pyroptosis related genes and subtypes in atherosclerosis using multiomic and single cell analysis |
| title_full_unstemmed | Identification of pyroptosis related genes and subtypes in atherosclerosis using multiomic and single cell analysis |
| title_short | Identification of pyroptosis related genes and subtypes in atherosclerosis using multiomic and single cell analysis |
| title_sort | identification of pyroptosis related genes and subtypes in atherosclerosis using multiomic and single cell analysis |
| topic | Atherosclerosis Pyroptosis TREM2 Multi-omics analysis Immune microenvironment |
| url | https://doi.org/10.1038/s41598-025-04398-2 |
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