Objective: Abdominal aortic aneurysms (AAAs) are characterized by inflammatory macrophage (M4) infiltration and pathologic vascular remodeling. The mechanisms regulating M4 polarization during AAA development remain unknown. There is increasing evidence that epigenetic enzymes, specifically the histone demethylase JMJD3, direct M4 polarization. The purpose of this study was to investigate whether JMJD3mediated epigenetic modifications regulate M4 inflammation and drive AAA formation.Methods: Single-cell RNA sequencing was conducted on human AAA and age-matched atherosclerotic control tissue samples. In addition, the angiotensin (Ang) II-induced AAA model was used to gain mechanistic insight. Briefly, after 4 weeks of high-fat diet, mice were infused with AngII or saline to induce AAAs. AAA maximum diameters were quantified and M4s were sorted. Messenger RNA abundance of inflammatory cytokines and Jmjd3 were determined by quantitative
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