Nε-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway
Background. Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. Nε-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam ce...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/1906204 |
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| author | Zhengyang Bao Lili Zhang Lihua Li Jinchuan Yan Qiwen Pang Zhen Sun Yue Geng Lele Jing Chen Shao Zhongqun Wang |
| author_facet | Zhengyang Bao Lili Zhang Lihua Li Jinchuan Yan Qiwen Pang Zhen Sun Yue Geng Lele Jing Chen Shao Zhongqun Wang |
| author_sort | Zhengyang Bao |
| collection | DOAJ |
| description | Background. Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. Nε-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic atherosclerosis is unknown. Methods and Results. In this study, we used anterior tibiofibular vascular samples from diabetic foot amputation patients and accident amputation patients, and histological and cytological tests were performed using a diabetic ApoE-/- mouse model and primary peritoneal macrophages, respectively. The results showed that the atherosclerotic plaques of diabetic foot amputation patients and diabetic ApoE-/- mice were larger than those of the control group. Inhibition of the Vav1/Rac1 pathway reduced vascular plaques and promoted the migration of macrophages to lymph nodes. Transwell and wound healing assays showed that the migratory ability of macrophage-derived foam cells was inhibited by CML. Cytoskeletal staining showed that advanced glycation end products inhibited the formation of lamellipodia in foam cells, and inhibition of the Vav1/Rac1 pathway restored the formation of lamellipodia. Conclusion. CML inhibits the migration of foam cells from blood vessels via the Vav1/Rac1 pathway, and this process affects the formation of lamellipodia. |
| format | Article |
| id | doaj-art-b98c490725fd4bf0866eff9a24e27398 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-b98c490725fd4bf0866eff9a24e273982025-02-03T01:26:58ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/19062041906204Nε-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 PathwayZhengyang Bao0Lili Zhang1Lihua Li2Jinchuan Yan3Qiwen Pang4Zhen Sun5Yue Geng6Lele Jing7Chen Shao8Zhongqun Wang9Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, ChinaDepartment of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, ChinaDepartment of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, ChinaBackground. Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. Nε-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic atherosclerosis is unknown. Methods and Results. In this study, we used anterior tibiofibular vascular samples from diabetic foot amputation patients and accident amputation patients, and histological and cytological tests were performed using a diabetic ApoE-/- mouse model and primary peritoneal macrophages, respectively. The results showed that the atherosclerotic plaques of diabetic foot amputation patients and diabetic ApoE-/- mice were larger than those of the control group. Inhibition of the Vav1/Rac1 pathway reduced vascular plaques and promoted the migration of macrophages to lymph nodes. Transwell and wound healing assays showed that the migratory ability of macrophage-derived foam cells was inhibited by CML. Cytoskeletal staining showed that advanced glycation end products inhibited the formation of lamellipodia in foam cells, and inhibition of the Vav1/Rac1 pathway restored the formation of lamellipodia. Conclusion. CML inhibits the migration of foam cells from blood vessels via the Vav1/Rac1 pathway, and this process affects the formation of lamellipodia.http://dx.doi.org/10.1155/2020/1906204 |
| spellingShingle | Zhengyang Bao Lili Zhang Lihua Li Jinchuan Yan Qiwen Pang Zhen Sun Yue Geng Lele Jing Chen Shao Zhongqun Wang Nε-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway Journal of Immunology Research |
| title | Nε-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway |
| title_full | Nε-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway |
| title_fullStr | Nε-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway |
| title_full_unstemmed | Nε-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway |
| title_short | Nε-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway |
| title_sort | nε carboxymethyl lysine negatively regulates foam cell migration via the vav1 rac1 pathway |
| url | http://dx.doi.org/10.1155/2020/1906204 |
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