The multifaceted therapeutic value of targeting ATP-citrate lyase in atherosclerosis

ATP-citrate lyase (Acly) is the target of the new class low-density lipoproteincholesterol (LDL-C)-lowering drug bempedoic acid (BA). Acly is a key metabolic enzyme synthesizing acetyl-CoA as the building block of cholesterol and fatty acids. Treatment with BA lowers circulating lipid levels and reduces systemic inflammation, suggesting a dual benefit of this drug for atherosclerosis therapy. Recent studies have shown that targeting Acly in macrophages can attenuate inflammatory responses and decrease atherosclerotic plaque vulnerability. Therefore, it could be beneficial to extend the application of Acly inhibition from solely lipid-lowering by liver-specific inhibition to also targeting macrophages in atherosclerosis. Here, we outline the possibilities of targeting Acly and describe the future needs to translate these findings to the clinic.

Automated summary

ATP-citrate lyase (ACLY) is a key metabolic enzyme that synthesizes acetyl-CoA, and is targeted by the new class low-density lipoprotein cholesterol (LDL-C)-lowering drug bempedoic acid (BA). Targeting ACLY in macrophages has been shown to attenuate inflammatory responses and reduce atherosclerotic plaque vulnerability, suggesting potential benefits in atherosclerosis therapy. Further research is needed to explore the translation of these findings into clinical applications.