IMMUNE-RESPONSIVE GENE 1 REGULATES ATHEROSCLEROTIC PLAQUE INFLAMMATION I

Atherosclerosis is the major underlying cause of cardiovascular disease (CVD) mortality and is fueled by a failure to resolve inflammation within the vessel wall1. The mechanisms underpinning sustained inflammation within this microenvironment are not fully elucidated. A more comprehensive understanding of the immunoregulatory pathways modulating inflammation in this context holds the potential to inform the development of more specific therapies. Immune responsive gene 1 (Irg1) is an enzyme that diverts cis-aconitate from the TCA cycle and produces the metabolite itaconate, which elicits immunological tolerance in the context of microbial infection2–4. We hypothesized that the IRG1-itaconate axis restricts inflammation in the atherosclerotic plaque. Overall design: PBMCs were treated with 4O1 and CVD plasma, plasma only or no plasma. After 4 hours, cells were harvest and subjected to scRNAseq ADT/HTO Barcode sequence hashtagged samples HT1 GTCAACTCTTTAGCG No_plasma_sample_1 HT2 TGATGGCCTATTGGG No_plasma_sample_2 HT3 TTCCGCCTCTCTTTG No_plasma_sample_3 HT4 AGTAAGTTCAGCGTA No_plasma_sample_4 HT1 GTCAACTCTTTAGCG plasma_sample_1 HT2 TGATGGCCTATTGGG plasma_sample_2 HT3 TTCCGCCTCTCTTTG plasma_sample_3 HT4 AGTAAGTTCAGCGTA plasma_sample_4 HT1 GTCAACTCTTTAGCG Plasma+4OI_sample_1 HT2 TGATGGCCTATTGGG Plasma+4OI_sample_2 HT3 TTCCGCCTCTCTTTG Plasma+4OI_sample_3 HT4 AGTAAGTTCAGCGTA Plasma+4OI_sample_4