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

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 (<i>ApoE</i> ^-/-) mice, in which increased expression of long-chain acyl-CoA synthetase 1 (<i>Acsl1</i>) in macrophages played an important role. Knockdown of <i>Acsl1</i> in macrophages (Mφ ^{<i>shAcsl1</i>} ) reprogrammed macrophages to an anti-inflammatory phenotype, especially under hyperglycemic conditions. Injection of Mφ ^{<i>shAcsl1</i>} reprogrammed macrophages into streptozotocin (STZ)-induced diabetic <i>ApoE</i> ^-/- mice (<i>ApoE</i> ^-/-+ 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 <i>Acsl1</i> expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice, possibly by promoting inflammation. Adoptive transfer of <i>Acsl1</i> silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis.