Itaconate suppresses atherosclerosis by impeding inflammation through Nrf2 signaling

Itaconate has emerged as a critical immunoregulatory metabolite. Here, we examined the therapeutic potential of itaconate in atherosclerosis. We found that both itaconate and the enzyme that synthesizes it, aconitate decarboxylase 1 (Acod1, also known as “immune-responsive gene 1”/IRG1) are upregulated during atherogenesis in mice. Here we analzyed the anatomy of atherosclerotic plaques from wildtype and Acod1-/- mice through single cell RNA-seq. Wildtype and and Acod1-/- mice were injected with recombinant PCSK9-AAV intraperitoneally. 1 week after the injection, mice were given western diet for 10 weeks to increase cholesterol level and promote atherosclerosis. Aorta samples with atherosclerotic plaques from WT and Acod1-/- mice were analyzed by single cell RNA sequencing using the droplet based 10X Genomics pipeline.