ATP-citrate lyase (ACLY) is a cytosolic enzyme and cleaves citrate in to oxaloacetate and acetyl-CoA. Cytosolic acetyl-CoA synthesized by ACLY serves several metabolic pathways, including the de novo synthesis of fatty acids and cholesterol. Specific inhibition of ACLY in hepatocytes has recently emerged as an attractive therapeutic target to lower lipid levels in hypercholesteremic patients. Additionally, ACLY was previously linked to macrophage activation. Here, using a novel myeloid-specific genetic knockdown model of ACLY we investigated the role of this enzyme in macrophages in atherosclerosis.

05 - MACROPHAGE ATP-CITRATE LYASE (ACLY) DEFICIENCY AFFECTS CELLULAR CHOLESTEROL HOMEOSTASIS AND STABILIZES ATHEROSCLEROTIC LESIONS