Drug screen identifies verteporfin as a regulator of lipid metabolism in macrophage foam cells

Arterial macrophage foam cells are filled with cholesterol ester (CE) stored in cytosolic lipid droplets (LDs). Foam cells are central players in progression of atherosclerosis as regulators of lipid metabolism and inflammation, two major driving forces of atherosclerosis development. Thus, foam cel...

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Bibliographic Details
Published in:Scientific reports 2023-11, Vol.13 (1), p.19588-19588, Article 19588
Main Authors: Hoeffner, Nicholas, Paul, Antoni, Goo, Young-Hwa
Format: Article
Language:English
Subjects:
692/4019
692/699
Arteriosclerosis
Atherosclerosis
Cholesterol
Drug screening
Gene expression
Humanities and Social Sciences
Inflammation
Lipid metabolism
Lipids
Macrophages
Metabolism
multidisciplinary
Science
Science (multidisciplinary)
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Summary:Arterial macrophage foam cells are filled with cholesterol ester (CE) stored in cytosolic lipid droplets (LDs). Foam cells are central players in progression of atherosclerosis as regulators of lipid metabolism and inflammation, two major driving forces of atherosclerosis development. Thus, foam cells are considered plausible targets for intervention in atherosclerosis. However, a compound that directly regulates the lipid metabolism of LDs in the arterial foam cells has not yet been identified. In this study, we screened compounds that inhibit macrophage foam cell formation using a library of 2697 FDA-approved drugs. From the foam cells generated via loading of human oxidized low-density lipoprotein (oxLDL), we found 21 and 6 compounds that reduced and enhanced accumulations of lipids respectively. Among them, verteporfin most significantly reduced oxLDL-induced foam cell formation whereas it did not display a significant impact on foam cell formation induced by fatty acid. Mechanistically our data demonstrate that verteporfin acts via inhibition of oxLDL association with macrophages, reducing accumulation of CE. Interestingly, while other drugs that reduced foam cell formation did not have impact on pre-existing foam cells, verteporfin treatment significantly reduced their total lipids, CE, and pro-inflammatory gene expression. Together, our study identifies verteporfin as a novel regulator of foam cell lipid metabolism and inflammation and a potential compound for intervention in atherosclerosis.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-46467-4