Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE -/- mice

Tingting Wang; Yan Dong; Li Yao; Fan Lu; Chenxi Wen; Zhuo Wan; Li Fan; Zhelong Li; Te Bu; Mengying Wei; Xuekang Yang; Yi Zhang

doi:10.1016/j.bioactmat.2022.02.002

Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE ^-/- mice

Bioact Mater. 2022 Feb 15:16:82-94. doi: 10.1016/j.bioactmat.2022.02.002. eCollection 2022 Oct.

Authors

Tingting Wang^{1

2}, Yan Dong³, Li Yao⁴, Fan Lu⁵, Chenxi Wen², Zhuo Wan³, Li Fan^{1

2}, Zhelong Li⁶, Te Bu⁶, Mengying Wei⁵, Xuekang Yang², Yi Zhang¹

Affiliations

¹ Department of Equipment Division, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
² Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
³ Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
⁴ Department of Pathology, Xi'an No. 3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, 710018, People's Republic of China.
⁵ Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
⁶ Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of China.

Abstract

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 (Mφ ^shAcsl1 ) reprogrammed macrophages to an anti-inflammatory phenotype, especially under hyperglycemic conditions. Injection of Mφ ^shAcsl1 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.

Keywords: Acsl1; Adoptive transfer; Atherosclerosis; Diabetes; Macrophage.