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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Main Authors: Tingting Wang, Yan Dong, Li Yao, Fan Lu, Chenxi Wen, Zhuo Wan, Li Fan, Zhelong Li, Te Bu, Mengying Wei, Xuekang Yang, Yi Zhang
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2022-10-01
Series:Bioactive Materials
Subjects:
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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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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