α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescence
Abstract Myocardial infarction (MI) has high morbidity and mortality, and the macrophage senescence-associated secretory phenotype (SASP) plays a central role in M1 healing. α-Lipoic acid (ALA) alleviates MI by regulating the function of macrophages, although the relationship between ALA and macroph...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-92328-7 |
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| author | Yuchao Wang Yue Zheng Xiaoyu Liang Yun Chang Yanwu Liu Xian Cheng Meng Zhang Wenqing Gao Tong Li |
| author_facet | Yuchao Wang Yue Zheng Xiaoyu Liang Yun Chang Yanwu Liu Xian Cheng Meng Zhang Wenqing Gao Tong Li |
| author_sort | Yuchao Wang |
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| description | Abstract Myocardial infarction (MI) has high morbidity and mortality, and the macrophage senescence-associated secretory phenotype (SASP) plays a central role in M1 healing. α-Lipoic acid (ALA) alleviates MI by regulating the function of macrophages, although the relationship between ALA and macrophage senescence remains unclear. To investigate macrophage SASP in MI, we performed single-cell RNA sequencing (scRNA-seq) on the GEO GSE163465 dataset, along with qPCR and western blot analyses to assess SASP expression in macrophages subjected to hypoxia and ALA treatment. Immunofluorescence was used to detect SASP distribution. Coculture and animal experiments were performed to assess the therapeutic effects of ALA on macrophage senescence and cardiomyocyte ischemic injury. scRNA-seq revealed an age-independent senescent propensity of macrophages in MI. Increased expression of H2A.X, CCL7, IL1β, and CDKN1A, along with decreased SOD2 expression, confirmed that macrophage SASP occurred after hypoxia, with oxidative stress and energy metabolism involved in the process. ALA inhibited the degradation of SIRT1 and promoted the Nrf2 nuclear translocation, alleviating macrophage senescence and myocardial ischemic injury. Age-independent macrophage SASP occurred during MI. Macrophage SASP was induced by ROS and mitochondrial dysfunction. ALA alleviated SASP by decreasing ROS generation and autophagy flux while increasing SIRT1 levels, and Nrf2 nuclear translocation. ALA ameliorated MI injury. |
| format | Article |
| id | doaj-art-7ba261d7e6a14719a10ee5d88b8fdab6 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-7ba261d7e6a14719a10ee5d88b8fdab62025-08-20T02:17:13ZengNature PortfolioScientific Reports2045-23222025-04-0115111410.1038/s41598-025-92328-7α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescenceYuchao Wang0Yue Zheng1Xiaoyu Liang2Yun Chang3Yanwu Liu4Xian Cheng5Meng Zhang6Wenqing Gao7Tong Li8School of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversityDepartment of Heart Center, The Third Central Hospital of TianjinDepartment of Heart Center, The Third Central Hospital of TianjinDepartment of Heart Center, The Third Central Hospital of TianjinDepartment of Heart Center, The Third Central Hospital of TianjinDepartment of Heart Center, The Third Central Hospital of TianjinDepartment of Heart Center, The Third Central Hospital of TianjinSchool of Medicine, Nankai UniversityAbstract Myocardial infarction (MI) has high morbidity and mortality, and the macrophage senescence-associated secretory phenotype (SASP) plays a central role in M1 healing. α-Lipoic acid (ALA) alleviates MI by regulating the function of macrophages, although the relationship between ALA and macrophage senescence remains unclear. To investigate macrophage SASP in MI, we performed single-cell RNA sequencing (scRNA-seq) on the GEO GSE163465 dataset, along with qPCR and western blot analyses to assess SASP expression in macrophages subjected to hypoxia and ALA treatment. Immunofluorescence was used to detect SASP distribution. Coculture and animal experiments were performed to assess the therapeutic effects of ALA on macrophage senescence and cardiomyocyte ischemic injury. scRNA-seq revealed an age-independent senescent propensity of macrophages in MI. Increased expression of H2A.X, CCL7, IL1β, and CDKN1A, along with decreased SOD2 expression, confirmed that macrophage SASP occurred after hypoxia, with oxidative stress and energy metabolism involved in the process. ALA inhibited the degradation of SIRT1 and promoted the Nrf2 nuclear translocation, alleviating macrophage senescence and myocardial ischemic injury. Age-independent macrophage SASP occurred during MI. Macrophage SASP was induced by ROS and mitochondrial dysfunction. ALA alleviated SASP by decreasing ROS generation and autophagy flux while increasing SIRT1 levels, and Nrf2 nuclear translocation. ALA ameliorated MI injury.https://doi.org/10.1038/s41598-025-92328-7Myocardial infarctionMacrophagesscRNA-sequenceSenescenceOxidative stressInflammation |
| spellingShingle | Yuchao Wang Yue Zheng Xiaoyu Liang Yun Chang Yanwu Liu Xian Cheng Meng Zhang Wenqing Gao Tong Li α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescence Scientific Reports Myocardial infarction Macrophages scRNA-sequence Senescence Oxidative stress Inflammation |
| title | α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescence |
| title_full | α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescence |
| title_fullStr | α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescence |
| title_full_unstemmed | α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescence |
| title_short | α-Lipoic acid alleviate myocardial infarction by suppressing age-independent macrophage senescence |
| title_sort | α lipoic acid alleviate myocardial infarction by suppressing age independent macrophage senescence |
| topic | Myocardial infarction Macrophages scRNA-sequence Senescence Oxidative stress Inflammation |
| url | https://doi.org/10.1038/s41598-025-92328-7 |
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