Abstract
Accumulating evidence over the past decades has revealed an intricate relationship between dysregulation of cellular metabolism and the progression of atherosclerotic cardiovascular disease. However, an integrated understanding of dysregulated cellular metabolism in atherosclerotic cardiovascular disease and its potential value as a therapeutic target is missing. In this Review, we (1) summarize recent advances concerning the role of metabolic dysregulation during atherosclerosis progression in lesional cells, including endothelial cells, vascular smooth muscle cells, macrophages and T cells; (2) explore the complexity of metabolic cross-talk between these lesional cells; (3) highlight emerging technologies that promise to illuminate unknown aspects of metabolism in atherosclerosis; and (4) suggest strategies for targeting these underexplored metabolic alterations to mitigate atherosclerosis progression and stabilize rupture-prone atheromas with a potential new generation of cardiovascular therapeutics.
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Acknowledgements
We acknowledge funding from an American Heart Association Postdoctoral Fellowship (23POST1026505) to A.C.F.; a Louisiana State University Health Sciences Center, Shreveport and Center for Cardiovascular Diseases and Sciences Postdoctoral Fellowship to A.C.F.; a Louisiana State University Health Sciences Center, Shreveport, CIRP, and Chancellor’s Pathways Research Award to A.Y.J. and O.R.; Deutsche Forschungsgemeinschaft (NE 2574/1-1) to F.S.N.; National Institutes of Health R01 HL135582 to M.S.; P01 HL136275 and R35 HL145241 to K.L.; R00 HL150233, R01 DK134011 and R01 DK136685 to O.R.; R00 HL145131 and R01 HL167758 to A.Y.J.
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C.S., F.S.N. and B.C. contributed equally to the drafting of the manuscript. A.C.F. provided comments on specific sections. M.A.S., K.L., O.R. and A.Y.J. reviewed and edited the manuscript. A.Y.J. oversaw the development of the Review, incorporating comments, revisions and edits. All authors contributed to the Review and approved the final version for publication.
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K.L. is founder and co-owner of Atherovax and receives no compensation from Atherovax. No Atherovax funds were used in this study. O.R. is a scientific advisor at Diapin Therapeutics and receives no compensation from Diapin Therapeutics. No Diapin Therapeutics funds were used in this study. All other authors declare no competing interests.
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Stroope, C., Nettersheim, F.S., Coon, B. et al. Dysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities. Nat Metab 6, 617–638 (2024). https://doi.org/10.1038/s42255-024-01015-w
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DOI: https://doi.org/10.1038/s42255-024-01015-w
