IMMUNE-RESPONSIVE GENE 1 REGULATES ATHEROSCLEROTIC PLAQUE INFLAMMATION IIII

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. Formation of atherslerotic plaque was induced in mice by placing them on Western Diet. Aorta's were removed and single-cell suspensions of the aortic arch were made and CD45+ immune cells were isolated by staining (anti-CD45 PerCp-Cy5.5, BioLegend) and flow sorting viable (fixable viability dye e780, eBioscience) single cells on a Facs Aria II cytometer (BD) equipped with a 100 µm nozzle. Next scRNA seq was performed and analyzed.