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 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. Increased expression of Acsl1 in macrophages is responsible for the aggravated inflammation and thus exacerbated atherosclerosis. Knockdown of Acsl1 in macrophages reprograms the cell to anti-inflammatory phenotype. Adoptive transfer of the reprogrammed macrophages significantly represses inflammation and alleviates atherosclerosis in diabetic ApoE−/- mice. [Display omitted] 1Increased Acsl1 in macrophages is responsible for the exacerbated inflammation in diabetes2MφshAcsl1 is characterized as anti-inflammatory phenotype3Adoptive transfer of MφshAcsl1 alleviates atherosclerosis in diabetic ApoE−/- mice4MφshAcsl1 inhibits both local and systemic inflammation in vivo