High expression of PLA2G2A in fibroblasts plays a crucial role in the early progression of carotid atherosclerosis
Abstract Background In mouse models of atherosclerosis, knockout of the PLA2G2A gene has been shown to reduce the volume of atherosclerotic plaques. Clinical trials have demonstrated the potential of using the sPLA2 inhibitor Varespladib in combination with statins to reduce lipid levels. However, t...
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BMC
2024-10-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-05679-6 |
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| author | Xin Wang Shen Li Chen Liu Jiawei Zhao Gangfeng Ren Feng Zhang Xuyang Liu Shuang Cao Yuming Xu Zongping Xia |
| author_facet | Xin Wang Shen Li Chen Liu Jiawei Zhao Gangfeng Ren Feng Zhang Xuyang Liu Shuang Cao Yuming Xu Zongping Xia |
| author_sort | Xin Wang |
| collection | DOAJ |
| description | Abstract Background In mouse models of atherosclerosis, knockout of the PLA2G2A gene has been shown to reduce the volume of atherosclerotic plaques. Clinical trials have demonstrated the potential of using the sPLA2 inhibitor Varespladib in combination with statins to reduce lipid levels. However, this approach has not yielded the expected results in reducing the risk of cardiovascular events. Therefore, it is necessary to further investigate the mechanisms of PLA2G2A. Methods Single-cell transcriptome data from two sets of carotid plaques, combined with clinical patient information. were used to describe the expression characteristics of PLA2G2A in carotid plaques at different stages. In order to explore the mechanisms of PLA2G2A, we conducted enrichment analysis, cell–cell communication analysis and single-cell regulatory network inference and clustering analyses. We validated the above findings at the cellular level. Results Our findings indicate that PLA2G2A is primarily expressed in vascular fibroblasts and shows significant cell interactions with macrophages in the early-stage, especially in complement and inflammation-related pathways. We also found that serum sPLA2 levels have stronger diagnostic value in patients with mild carotid artery stenosis. Subsequent comparisons of single-cell transcriptomic data from early and late-stage carotid artery plaques corroborated these findings and predicted transcription factors that might regulate the progression of early carotid atherosclerosis (CA) and the expression of PLA2G2A. Conclusions Our study discovered and validated that PLA2G2A is highly expressed by vascular fibroblasts and promotes plaque progression through the activation of macrophage complement and coagulation cascade pathways in the early-stage of CA. |
| format | Article |
| id | doaj-art-39e438bfc66047b1a751b7ca8808a0e4 |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-39e438bfc66047b1a751b7ca8808a0e42025-08-20T02:11:47ZengBMCJournal of Translational Medicine1479-58762024-10-0122111510.1186/s12967-024-05679-6High expression of PLA2G2A in fibroblasts plays a crucial role in the early progression of carotid atherosclerosisXin Wang0Shen Li1Chen Liu2Jiawei Zhao3Gangfeng Ren4Feng Zhang5Xuyang Liu6Shuang Cao7Yuming Xu8Zongping Xia9The Clinical Systems Biology Laboratories of the First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou UniversityThe Clinical Systems Biology Laboratories of the First Affiliated Hospital of Zhengzhou UniversityThe Clinical Systems Biology Laboratories of the First Affiliated Hospital of Zhengzhou UniversityThe Clinical Systems Biology Laboratories of the First Affiliated Hospital of Zhengzhou UniversityThe Clinical Systems Biology Laboratories of the First Affiliated Hospital of Zhengzhou UniversityThe Clinical Systems Biology Laboratories of the First Affiliated Hospital of Zhengzhou UniversityThe Clinical Systems Biology Laboratories of the First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou UniversityThe Clinical Systems Biology Laboratories of the First Affiliated Hospital of Zhengzhou UniversityAbstract Background In mouse models of atherosclerosis, knockout of the PLA2G2A gene has been shown to reduce the volume of atherosclerotic plaques. Clinical trials have demonstrated the potential of using the sPLA2 inhibitor Varespladib in combination with statins to reduce lipid levels. However, this approach has not yielded the expected results in reducing the risk of cardiovascular events. Therefore, it is necessary to further investigate the mechanisms of PLA2G2A. Methods Single-cell transcriptome data from two sets of carotid plaques, combined with clinical patient information. were used to describe the expression characteristics of PLA2G2A in carotid plaques at different stages. In order to explore the mechanisms of PLA2G2A, we conducted enrichment analysis, cell–cell communication analysis and single-cell regulatory network inference and clustering analyses. We validated the above findings at the cellular level. Results Our findings indicate that PLA2G2A is primarily expressed in vascular fibroblasts and shows significant cell interactions with macrophages in the early-stage, especially in complement and inflammation-related pathways. We also found that serum sPLA2 levels have stronger diagnostic value in patients with mild carotid artery stenosis. Subsequent comparisons of single-cell transcriptomic data from early and late-stage carotid artery plaques corroborated these findings and predicted transcription factors that might regulate the progression of early carotid atherosclerosis (CA) and the expression of PLA2G2A. Conclusions Our study discovered and validated that PLA2G2A is highly expressed by vascular fibroblasts and promotes plaque progression through the activation of macrophage complement and coagulation cascade pathways in the early-stage of CA.https://doi.org/10.1186/s12967-024-05679-6Carotid atherosclerosisSingle-cell transcriptomeFibroblastComplement and coagulation cascade pathwaySecretory phospholipase A2 |
| spellingShingle | Xin Wang Shen Li Chen Liu Jiawei Zhao Gangfeng Ren Feng Zhang Xuyang Liu Shuang Cao Yuming Xu Zongping Xia High expression of PLA2G2A in fibroblasts plays a crucial role in the early progression of carotid atherosclerosis Journal of Translational Medicine Carotid atherosclerosis Single-cell transcriptome Fibroblast Complement and coagulation cascade pathway Secretory phospholipase A2 |
| title | High expression of PLA2G2A in fibroblasts plays a crucial role in the early progression of carotid atherosclerosis |
| title_full | High expression of PLA2G2A in fibroblasts plays a crucial role in the early progression of carotid atherosclerosis |
| title_fullStr | High expression of PLA2G2A in fibroblasts plays a crucial role in the early progression of carotid atherosclerosis |
| title_full_unstemmed | High expression of PLA2G2A in fibroblasts plays a crucial role in the early progression of carotid atherosclerosis |
| title_short | High expression of PLA2G2A in fibroblasts plays a crucial role in the early progression of carotid atherosclerosis |
| title_sort | high expression of pla2g2a in fibroblasts plays a crucial role in the early progression of carotid atherosclerosis |
| topic | Carotid atherosclerosis Single-cell transcriptome Fibroblast Complement and coagulation cascade pathway Secretory phospholipase A2 |
| url | https://doi.org/10.1186/s12967-024-05679-6 |
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