Quercetin ameliorates ox-LDL-induced cellular senescence of aortic endothelial cells and macrophages by p16/p21, p53/SERPINE1, and AMPK/mTOR pathways
Abstract Background Atherosclerosis (AS), a chronic inflammatory disease of the arterial wall, remains a dominant cause of death and disability globally. Quercetin has been evidenced to be effective against AS, but the exact mechanisms are still largely unclear. Methods Oxidized low-density lipoprot...
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2025-05-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02562-y |
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| author | Xiao Liang Jingyuan Zhang Jiangbo Yu Jiyi Zhao Shusen Yang |
| author_facet | Xiao Liang Jingyuan Zhang Jiangbo Yu Jiyi Zhao Shusen Yang |
| author_sort | Xiao Liang |
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| description | Abstract Background Atherosclerosis (AS), a chronic inflammatory disease of the arterial wall, remains a dominant cause of death and disability globally. Quercetin has been evidenced to be effective against AS, but the exact mechanisms are still largely unclear. Methods Oxidized low-density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs) and mouse RAW264.7 macrophages were established, with quercetin treatment or p16, p21 or SERPINE1 siRNA transfection. Cellular senescence was assessed by SA-β-gal staining and detection of cellular senescence markers. Cell cycle, apoptosis and intracellular ROS were detected by flow cytometry, with cell proliferation by CCK-8. Lipid accumulation was assessed utilizing oil red O staining. Through transmission electron microscope, autophagosomes and mitochondria were investigated, with detection of autophagy markers. Finally, AS models of ApoE−/− mice were established through feeding high-fat diet, and the effect of quercetin on alleviating AS progression was investigated. Results Quercetin protected HAECs from ox-LDL-elicited senescent phenotype, growth arrest and apoptosis and promoted cell viability in a concentration-dependent fashion. Furthermore, quercetin alleviated ox-LDL-elicited cellular senescence, ROS and lipid accumulation in macrophages. In ox-LDL-induced HAECs or/and macrophages, quercetin down-regulated the expression of p16, p21, p53 and SERPINE1, elevated p-AMPK/AMPK levels and decreased p-mTOR/mTOR levels, and these effects of quercetin were ameliorated by SERPINE1 knockdown. In AS mouse models, quercetin treatment alleviated AS progression. Conclusion Our findings proposed a novel anti-atherosclerotic mechanism of quercetin by mitigating ox-LDL-elicited senescent phenotype of aortic endothelial cells and macrophages by regulating p16/p21, p53/SERPINE1, and AMPK/mTOR pathways. |
| format | Article |
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| language | English |
| publishDate | 2025-05-01 |
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| series | European Journal of Medical Research |
| spelling | doaj-art-c2e50fc187a947d49a95294cdd2785ed2025-08-20T02:11:22ZengBMCEuropean Journal of Medical Research2047-783X2025-05-0130112010.1186/s40001-025-02562-yQuercetin ameliorates ox-LDL-induced cellular senescence of aortic endothelial cells and macrophages by p16/p21, p53/SERPINE1, and AMPK/mTOR pathwaysXiao Liang0Jingyuan Zhang1Jiangbo Yu2Jiyi Zhao3Shusen Yang4Department of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Zhejiang University School of MedicineDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityAbstract Background Atherosclerosis (AS), a chronic inflammatory disease of the arterial wall, remains a dominant cause of death and disability globally. Quercetin has been evidenced to be effective against AS, but the exact mechanisms are still largely unclear. Methods Oxidized low-density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs) and mouse RAW264.7 macrophages were established, with quercetin treatment or p16, p21 or SERPINE1 siRNA transfection. Cellular senescence was assessed by SA-β-gal staining and detection of cellular senescence markers. Cell cycle, apoptosis and intracellular ROS were detected by flow cytometry, with cell proliferation by CCK-8. Lipid accumulation was assessed utilizing oil red O staining. Through transmission electron microscope, autophagosomes and mitochondria were investigated, with detection of autophagy markers. Finally, AS models of ApoE−/− mice were established through feeding high-fat diet, and the effect of quercetin on alleviating AS progression was investigated. Results Quercetin protected HAECs from ox-LDL-elicited senescent phenotype, growth arrest and apoptosis and promoted cell viability in a concentration-dependent fashion. Furthermore, quercetin alleviated ox-LDL-elicited cellular senescence, ROS and lipid accumulation in macrophages. In ox-LDL-induced HAECs or/and macrophages, quercetin down-regulated the expression of p16, p21, p53 and SERPINE1, elevated p-AMPK/AMPK levels and decreased p-mTOR/mTOR levels, and these effects of quercetin were ameliorated by SERPINE1 knockdown. In AS mouse models, quercetin treatment alleviated AS progression. Conclusion Our findings proposed a novel anti-atherosclerotic mechanism of quercetin by mitigating ox-LDL-elicited senescent phenotype of aortic endothelial cells and macrophages by regulating p16/p21, p53/SERPINE1, and AMPK/mTOR pathways.https://doi.org/10.1186/s40001-025-02562-yQuercetinAtherosclerosisCellular senescenceAortic endothelial cellsMacrophagesAutophagy |
| spellingShingle | Xiao Liang Jingyuan Zhang Jiangbo Yu Jiyi Zhao Shusen Yang Quercetin ameliorates ox-LDL-induced cellular senescence of aortic endothelial cells and macrophages by p16/p21, p53/SERPINE1, and AMPK/mTOR pathways European Journal of Medical Research Quercetin Atherosclerosis Cellular senescence Aortic endothelial cells Macrophages Autophagy |
| title | Quercetin ameliorates ox-LDL-induced cellular senescence of aortic endothelial cells and macrophages by p16/p21, p53/SERPINE1, and AMPK/mTOR pathways |
| title_full | Quercetin ameliorates ox-LDL-induced cellular senescence of aortic endothelial cells and macrophages by p16/p21, p53/SERPINE1, and AMPK/mTOR pathways |
| title_fullStr | Quercetin ameliorates ox-LDL-induced cellular senescence of aortic endothelial cells and macrophages by p16/p21, p53/SERPINE1, and AMPK/mTOR pathways |
| title_full_unstemmed | Quercetin ameliorates ox-LDL-induced cellular senescence of aortic endothelial cells and macrophages by p16/p21, p53/SERPINE1, and AMPK/mTOR pathways |
| title_short | Quercetin ameliorates ox-LDL-induced cellular senescence of aortic endothelial cells and macrophages by p16/p21, p53/SERPINE1, and AMPK/mTOR pathways |
| title_sort | quercetin ameliorates ox ldl induced cellular senescence of aortic endothelial cells and macrophages by p16 p21 p53 serpine1 and ampk mtor pathways |
| topic | Quercetin Atherosclerosis Cellular senescence Aortic endothelial cells Macrophages Autophagy |
| url | https://doi.org/10.1186/s40001-025-02562-y |
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