Bioactive Materials (Oct 2022)

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

Journal volume & issue
Vol. 16
pp. 82 – 94

Abstract

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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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