Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells
1
Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA
2
Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(15), 3784; https://doi.org/10.3390/ijms20153784
Received: 3 July 2019 / Revised: 29 July 2019 / Accepted: 30 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future)
Arterial foam cells are central players of atherogenesis. Cholesterol acceptors, apolipoprotein A-I (apoA-I) and high-density lipoprotein (HDL), take up cholesterol and phospholipids effluxed from foam cells into the circulation. Due to the high abundance of cholesterol in foam cells, most previous studies focused on apoA-I/HDL-mediated free cholesterol (FC) transport. However, recent lipidomics of human atherosclerotic plaques also identified that oxidized sterols (oxysterols) and non-sterol lipid species accumulate as atherogenesis progresses. While it is known that these lipids regulate expression of pro-inflammatory genes linked to plaque instability, how cholesterol acceptors impact the foam cell lipidome, particularly oxysterols and non-sterol lipids, remains unexplored. Using lipidomics analyses, we found cholesterol acceptors remodel foam cell lipidomes. Lipid subclass analyses revealed various oxysterols, sphingomyelins, and ceramides, species uniquely enriched in human plaques were significantly reduced by cholesterol acceptors, especially by apoA-I. These results indicate that the function of lipid-poor apoA-I is not limited to the efflux of cholesterol and phospholipids but suggest that apoA-I serves as a major regulator of the foam cell lipidome and might play an important role in reducing multiple lipid species involved in the pathogenesis of atherosclerosis.
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Keywords:
ABCA1; ABCG1; cholesterol; macrophage; foam cells; atherosclerosis; LDL; lipidome; lipidomics; mass-spectrometry; oxysterols; reverse cholesterol transport
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MDPI and ACS Style
Paul, A.; Lydic, T.A.; Hogan, R.; Goo, Y.-H. Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells. Int. J. Mol. Sci. 2019, 20, 3784. https://doi.org/10.3390/ijms20153784
AMA Style
Paul A, Lydic TA, Hogan R, Goo Y-H. Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells. International Journal of Molecular Sciences. 2019; 20(15):3784. https://doi.org/10.3390/ijms20153784
Chicago/Turabian StylePaul, Antoni, Todd A. Lydic, Ryan Hogan, and Young-Hwa Goo. 2019. "Cholesterol Acceptors Regulate the Lipidome of Macrophage Foam Cells" International Journal of Molecular Sciences 20, no. 15: 3784. https://doi.org/10.3390/ijms20153784
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