Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE−/- mice
Atherosclerosis is characterized by inflammation in the arterial wall, which is known to be exacerbated by diabetes. Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis. In this study, we showed that diabetes aggravated atherosclerosis in apolipoproteinE knock...
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KeAi Communications Co., Ltd.
2022-10-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X22000676 |
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author | Tingting Wang Yan Dong Li Yao Fan Lu Chenxi Wen Zhuo Wan Li Fan Zhelong Li Te Bu Mengying Wei Xuekang Yang Yi Zhang |
author_facet | Tingting Wang Yan Dong Li Yao Fan Lu Chenxi Wen Zhuo Wan Li Fan Zhelong Li Te Bu Mengying Wei Xuekang Yang Yi Zhang |
author_sort | Tingting Wang |
collection | DOAJ |
description | Atherosclerosis is characterized by inflammation in the arterial wall, which is known to be exacerbated by diabetes. Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis. In this study, we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout (ApoE−/-) mice, in which increased expression of long-chain acyl-CoA synthetase 1 (Acsl1) in macrophages played an important role. Knockdown of Acsl1 in macrophages (MφshAcsl1) reprogrammed macrophages to an anti-inflammatory phenotype, especially under hyperglycemic conditions. Injection of MφshAcsl1 reprogrammed macrophages into streptozotocin (STZ)-induced diabetic ApoE−/- mice (ApoE−/-+ STZ) alleviated inflammation locally in the plaque, liver and spleen. Consistent with the reduction in inflammation, plaques became smaller and more stable after the adoptive transfer of reprogrammed macrophages. Taken together, our findings indicate that increased Acsl1 expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice, possibly by promoting inflammation. Adoptive transfer of Acsl1 silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis. |
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issn | 2452-199X |
language | English |
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spelling | doaj.art-332980c8b6ff4a1da56d71915ea1a50b2024-04-17T00:44:13ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-10-01168294Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE−/- miceTingting Wang0Yan Dong1Li Yao2Fan Lu3Chenxi Wen4Zhuo Wan5Li Fan6Zhelong Li7Te Bu8Mengying Wei9Xuekang Yang10Yi Zhang11Department of Equipment Division, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, People's Republic of China; Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of ChinaDepartment of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of ChinaDepartment of Pathology, Xi'an No. 3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, 710018, People's Republic of ChinaDepartment of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, People's Republic of ChinaDepartment of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of ChinaDepartment of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of ChinaDepartment of Equipment Division, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, People's Republic of China; Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of ChinaDepartment of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of ChinaDepartment of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of ChinaDepartment of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, People's Republic of China; Corresponding author.Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China; Corresponding author.Department of Equipment Division, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, People's Republic of China; Corresponding author.Atherosclerosis is characterized by inflammation in the arterial wall, which is known to be exacerbated by diabetes. Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis. In this study, we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout (ApoE−/-) mice, in which increased expression of long-chain acyl-CoA synthetase 1 (Acsl1) in macrophages played an important role. Knockdown of Acsl1 in macrophages (MφshAcsl1) reprogrammed macrophages to an anti-inflammatory phenotype, especially under hyperglycemic conditions. Injection of MφshAcsl1 reprogrammed macrophages into streptozotocin (STZ)-induced diabetic ApoE−/- mice (ApoE−/-+ STZ) alleviated inflammation locally in the plaque, liver and spleen. Consistent with the reduction in inflammation, plaques became smaller and more stable after the adoptive transfer of reprogrammed macrophages. Taken together, our findings indicate that increased Acsl1 expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice, possibly by promoting inflammation. Adoptive transfer of Acsl1 silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis.http://www.sciencedirect.com/science/article/pii/S2452199X22000676AtherosclerosisDiabetesMacrophageAcsl1Adoptive transfer |
spellingShingle | Tingting Wang Yan Dong Li Yao Fan Lu Chenxi Wen Zhuo Wan Li Fan Zhelong Li Te Bu Mengying Wei Xuekang Yang Yi Zhang Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE−/- mice Bioactive Materials Atherosclerosis Diabetes Macrophage Acsl1 Adoptive transfer |
title | Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE−/- mice |
title_full | Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE−/- mice |
title_fullStr | Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE−/- mice |
title_full_unstemmed | Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE−/- mice |
title_short | Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE−/- mice |
title_sort | adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic apoe mice |
topic | Atherosclerosis Diabetes Macrophage Acsl1 Adoptive transfer |
url | http://www.sciencedirect.com/science/article/pii/S2452199X22000676 |
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