Taken together, our results indicate that constitutive genetic inactivation of Acod1 exacerbates hypercholesterolemia-induced inflammation and atherogenesis, associated with increased lesion size, elevated macrophage infiltration, elevated peripheral neutrophils and monocytes, and higher expression of proinflammatory cytokines and chemokines. Here, ACOD1 is linked to Hypercholesterolemia.