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

Sanne G. S. Verberk, Kirsten L. Kuiper, Mario A. Lauterbach, Eicke Latz, Jan van den Bossche*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

ATP-citrate lyase (Acly) is the target of the new class low-density lipoprotein-cholesterol (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.
Original languageEnglish
Number of pages11
JournalTrends in Molecular Medicine
Volume27
Issue number12
Early online date2021
DOIs
Publication statusPublished - Dec 2021

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