Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization
Abstract Vascular restenosis is a serious clinical issue initiated and aggravated by macrophage inflammation, with no effective treatments available, in cardiovascular and autoimmune diseases. However, the untapped mechanisms and new targets that can regulate macrophage polarization and vascular res...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408992 |
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| author | Jinlin Miao Yule Yong Zhaohui Zheng Kui Zhang Wei Li Jiayi Liu Siyi Zhou Juan‐juan Qin Haoyang Sun Yatao Wang Xianghui Fu Xing Luo Siyu Chen Zhi‐Gang She Jingjing Cai Ping Zhu |
| author_facet | Jinlin Miao Yule Yong Zhaohui Zheng Kui Zhang Wei Li Jiayi Liu Siyi Zhou Juan‐juan Qin Haoyang Sun Yatao Wang Xianghui Fu Xing Luo Siyu Chen Zhi‐Gang She Jingjing Cai Ping Zhu |
| author_sort | Jinlin Miao |
| collection | DOAJ |
| description | Abstract Vascular restenosis is a serious clinical issue initiated and aggravated by macrophage inflammation, with no effective treatments available, in cardiovascular and autoimmune diseases. However, the untapped mechanisms and new targets that can regulate macrophage polarization and vascular restenosis remain elusive. The research identifies interferon regulatory factor 4 (IRF4) expression as crucial in macrophage polarization during arterial restenosis. Myeloid‐specific Irf4 deficiency and overexpression experiments showed that IRF4 promoted M2 macrophage polarization, inhibited M1 macrophage transitions, and disrupted the interaction between macrophages and vascular smooth muscle cells to reduce neointimal hyperplasia by directly upregulating krüppel like factor 4 (KLF4) expression. Artesunate, an FDA‐approved drug, is screened as a potent activator of IRF4 expression in M2 polarization, and its treatment attenuated arterial restenosis in rodents and non‐human primates. The findings reveal a significant protective role of IRF4 in the development of neointimal hyperplasia by regulating macrophage polarization, and artesunate may be proposed as a novel therapy for vascular restenosis. |
| format | Article |
| id | doaj-art-200fcee4f9f74260a08a38f006563f32 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-200fcee4f9f74260a08a38f006563f322025-08-20T03:13:30ZengWileyAdvanced Science2198-38442025-05-011219n/an/a10.1002/advs.202408992Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage PolarizationJinlin Miao0Yule Yong1Zhaohui Zheng2Kui Zhang3Wei Li4Jiayi Liu5Siyi Zhou6Juan‐juan Qin7Haoyang Sun8Yatao Wang9Xianghui Fu10Xing Luo11Siyu Chen12Zhi‐Gang She13Jingjing Cai14Ping Zhu15Department of Clinical Immunology of Xijing Hospital and Department of Cell Biology of National Translational Science Center for Molecular Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Clinical Immunology of Xijing Hospital and Department of Cell Biology of National Translational Science Center for Molecular Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Clinical Immunology of Xijing Hospital and Department of Cell Biology of National Translational Science Center for Molecular Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Clinical Immunology of Xijing Hospital and Department of Cell Biology of National Translational Science Center for Molecular Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Cardiology Renmin Hospital Wuhan University Wuhan 430060 ChinaDepartment of Cardiology Renmin Hospital Wuhan University Wuhan 430060 ChinaInstitute of Model Animal Wuhan University Wuhan 430071 ChinaDepartment of Geriatrics Zhongnan Hospital Wuhan University Wuhan 430070 ChinaDepartment of Clinical Immunology of Xijing Hospital and Department of Cell Biology of National Translational Science Center for Molecular Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Clinical Immunology of Xijing Hospital and Department of Cell Biology of National Translational Science Center for Molecular Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Clinical Immunology of Xijing Hospital and Department of Cell Biology of National Translational Science Center for Molecular Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Clinical Immunology of Xijing Hospital and Department of Cell Biology of National Translational Science Center for Molecular Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Clinical Immunology of Xijing Hospital and Department of Cell Biology of National Translational Science Center for Molecular Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Cardiology Renmin Hospital Wuhan University Wuhan 430060 ChinaDepartment of Cardiology The Third Xiangya Hospital Central South University Changsha 410013 ChinaDepartment of Clinical Immunology of Xijing Hospital and Department of Cell Biology of National Translational Science Center for Molecular Medicine Fourth Military Medical University Xi'an 710032 ChinaAbstract Vascular restenosis is a serious clinical issue initiated and aggravated by macrophage inflammation, with no effective treatments available, in cardiovascular and autoimmune diseases. However, the untapped mechanisms and new targets that can regulate macrophage polarization and vascular restenosis remain elusive. The research identifies interferon regulatory factor 4 (IRF4) expression as crucial in macrophage polarization during arterial restenosis. Myeloid‐specific Irf4 deficiency and overexpression experiments showed that IRF4 promoted M2 macrophage polarization, inhibited M1 macrophage transitions, and disrupted the interaction between macrophages and vascular smooth muscle cells to reduce neointimal hyperplasia by directly upregulating krüppel like factor 4 (KLF4) expression. Artesunate, an FDA‐approved drug, is screened as a potent activator of IRF4 expression in M2 polarization, and its treatment attenuated arterial restenosis in rodents and non‐human primates. The findings reveal a significant protective role of IRF4 in the development of neointimal hyperplasia by regulating macrophage polarization, and artesunate may be proposed as a novel therapy for vascular restenosis.https://doi.org/10.1002/advs.202408992artesunateIRF4macrophagesneointimal hyperplasiarestenosis |
| spellingShingle | Jinlin Miao Yule Yong Zhaohui Zheng Kui Zhang Wei Li Jiayi Liu Siyi Zhou Juan‐juan Qin Haoyang Sun Yatao Wang Xianghui Fu Xing Luo Siyu Chen Zhi‐Gang She Jingjing Cai Ping Zhu Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization Advanced Science artesunate IRF4 macrophages neointimal hyperplasia restenosis |
| title | Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization |
| title_full | Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization |
| title_fullStr | Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization |
| title_full_unstemmed | Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization |
| title_short | Artesunate Inhibits Neointimal Hyperplasia by Promoting IRF4 Associated Macrophage Polarization |
| title_sort | artesunate inhibits neointimal hyperplasia by promoting irf4 associated macrophage polarization |
| topic | artesunate IRF4 macrophages neointimal hyperplasia restenosis |
| url | https://doi.org/10.1002/advs.202408992 |
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