NCOA4 linked to endothelial cell ferritinophagy and ferroptosis:a key regulator aggravate aortic endothelial inflammation and atherosclerosis
Atherosclerosis (AS) is associated with a high incidence of cardiovascular events, yet the mechanisms underlying this association remain unclear. Our previous study found that Atherosclerotic endothelial injury is closely associated with ferroptosis in ApoE−/− mice. Ferroptosis is a novel mode of ce...
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Elsevier
2025-02-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004439 |
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| author | Li Zhu Zijian Liu Jiahui Liu Zhenglong Li Youli Bao Xin Sun Wenchen Zhao An Zhou Hongfei Wu |
| author_facet | Li Zhu Zijian Liu Jiahui Liu Zhenglong Li Youli Bao Xin Sun Wenchen Zhao An Zhou Hongfei Wu |
| author_sort | Li Zhu |
| collection | DOAJ |
| description | Atherosclerosis (AS) is associated with a high incidence of cardiovascular events, yet the mechanisms underlying this association remain unclear. Our previous study found that Atherosclerotic endothelial injury is closely associated with ferroptosis in ApoE−/− mice. Ferroptosis is a novel mode of cell death induced by decreased antioxidant capacity of the organism and accumulation of reactive oxygen species. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is an important regulator of sudden ferroptosis in cells. However, the role of NCOA4 in AS and the exact mechanism by which it regulates the ferritinophagy response remain unclear. Herein, we report that NCOA4 expression is elevated in ApoE−/− mice and endothelial cells and is significantly correlated with AS. NCOA4 expression promoted ferroptosis, and was positively correlated with ferritinophagy response. Mechanistically, our findings indicate that LOX-1 is a key upstream target that influences the function of NCOA4. The specific pathway is related to the activation of cGAS-STING signaling to upregulate NCOA4 expression. Moreover, our findings demonstrate the ''Gualou-Xiebai'' herb pair can regulate LOX-1 to inhibit ferroptosis. Collectively, our results provide evidence of a connection between NCOA4-mediated promotion of AS and suggest that targeting upstream molecules regulating NCOA4 could be a potential therapy for AS. |
| format | Article |
| id | doaj-art-385914618b4345adab79466e192f2c24 |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-385914618b4345adab79466e192f2c242025-01-14T04:12:10ZengElsevierRedox Biology2213-23172025-02-0179103465NCOA4 linked to endothelial cell ferritinophagy and ferroptosis:a key regulator aggravate aortic endothelial inflammation and atherosclerosisLi Zhu0Zijian Liu1Jiahui Liu2Zhenglong Li3Youli Bao4Xin Sun5Wenchen Zhao6An Zhou7Hongfei Wu8School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural ProductsSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural ProductsSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural ProductsSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural ProductsSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural ProductsSchool of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural ProductsDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, 15219, USAAnhui Province Key Laboratory of Bioactive Natural Products; Corresponding author.School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China; Anhui Province Key Laboratory of Bioactive Natural Products; Corresponding author. School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China.Atherosclerosis (AS) is associated with a high incidence of cardiovascular events, yet the mechanisms underlying this association remain unclear. Our previous study found that Atherosclerotic endothelial injury is closely associated with ferroptosis in ApoE−/− mice. Ferroptosis is a novel mode of cell death induced by decreased antioxidant capacity of the organism and accumulation of reactive oxygen species. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is an important regulator of sudden ferroptosis in cells. However, the role of NCOA4 in AS and the exact mechanism by which it regulates the ferritinophagy response remain unclear. Herein, we report that NCOA4 expression is elevated in ApoE−/− mice and endothelial cells and is significantly correlated with AS. NCOA4 expression promoted ferroptosis, and was positively correlated with ferritinophagy response. Mechanistically, our findings indicate that LOX-1 is a key upstream target that influences the function of NCOA4. The specific pathway is related to the activation of cGAS-STING signaling to upregulate NCOA4 expression. Moreover, our findings demonstrate the ''Gualou-Xiebai'' herb pair can regulate LOX-1 to inhibit ferroptosis. Collectively, our results provide evidence of a connection between NCOA4-mediated promotion of AS and suggest that targeting upstream molecules regulating NCOA4 could be a potential therapy for AS.http://www.sciencedirect.com/science/article/pii/S2213231724004439Nuclear receptor coactivator 4FerritinophagyFerroptosisEndothelial injuryAtherosclerosis“Gualou-Xiebai” herb pair |
| spellingShingle | Li Zhu Zijian Liu Jiahui Liu Zhenglong Li Youli Bao Xin Sun Wenchen Zhao An Zhou Hongfei Wu NCOA4 linked to endothelial cell ferritinophagy and ferroptosis:a key regulator aggravate aortic endothelial inflammation and atherosclerosis Redox Biology Nuclear receptor coactivator 4 Ferritinophagy Ferroptosis Endothelial injury Atherosclerosis “Gualou-Xiebai” herb pair |
| title | NCOA4 linked to endothelial cell ferritinophagy and ferroptosis:a key regulator aggravate aortic endothelial inflammation and atherosclerosis |
| title_full | NCOA4 linked to endothelial cell ferritinophagy and ferroptosis:a key regulator aggravate aortic endothelial inflammation and atherosclerosis |
| title_fullStr | NCOA4 linked to endothelial cell ferritinophagy and ferroptosis:a key regulator aggravate aortic endothelial inflammation and atherosclerosis |
| title_full_unstemmed | NCOA4 linked to endothelial cell ferritinophagy and ferroptosis:a key regulator aggravate aortic endothelial inflammation and atherosclerosis |
| title_short | NCOA4 linked to endothelial cell ferritinophagy and ferroptosis:a key regulator aggravate aortic endothelial inflammation and atherosclerosis |
| title_sort | ncoa4 linked to endothelial cell ferritinophagy and ferroptosis a key regulator aggravate aortic endothelial inflammation and atherosclerosis |
| topic | Nuclear receptor coactivator 4 Ferritinophagy Ferroptosis Endothelial injury Atherosclerosis “Gualou-Xiebai” herb pair |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004439 |
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