Macrophage metabolism in atherosclerosis
Abstract
A key aspect of atherosclerosis is the maladaptive inflammatory response to lipoprotein accumulation in the artery. The failure to decrease lipid accumulation, to clear apoptotic cells, and to resolve inflammation ultimately leads to macrophage accumulation within the vascular wall [Thorp EB (2010) Apoptosis 15, 1124–1136; Moore K et al. (2013) Nat Rev Immunol 13, 709–721; Moore KJ and Tabas I (2011) Cell 145, 341–355; Ley K et al. (2011) Arterioscler Thromb Vasc Biol 31, 1506–1516]. Several subsets of macrophages are found inside atherosclerotic plaques [Chinetti‐Gbaguidi G et al. (2015) Nat Rev Cardiol 12, 10–17; Leitinger N and Schulman IG (2013) Arterioscler Thromb Vasc Biol 33, 1120–1126; Mantovani A et al. (2009) Arterioscler Thromb Vasc Biol 29, 1419–1423]: Proinflammatory M1‐like macrophages potentially participate in atherosclerosis initiation and progression; M2‐like macrophages are thought to be protective due to their anti‐inflammatory and profibrotic properties, presumably stabilizing the plaque [Chistiakov DA et al. (2015) Int J Cardiol 184, 436–445; Gordon S (2003) Nat Rev Immunol 3, 23–35]; Mox macrophages develop in response to oxidized phospholipids and present a glutathione‐ and potentially redox‐regulating phenotype [Kadl A et al. (2010) Circ Res 107, 737–746]; Mhem macrophages are found in areas of plaque hemorrhage [Boyle JJ et al. (2009) Am J Pathol 174, 1097–1108; Boyle JJ et al. (2012) Circ Res 110, 20–33] where they are involved in heme clearance. Recent evidence suggests that the relative abundance of these macrophage subsets is a better indicator of plaque progression and stability than the total number of lesion macrophages [Chinetti‐Gbaguidi G et al. (2015) Nat Rev Cardiol 12, 10–17]. Over the last few years, findings in the area of immunometabolism established a link between the metabolic state of the different macrophage phenotypes and their functions [O'Neill LAJ and Pearce EJ (2016) J Exp Med 213, 15–23]. However, the effect of metabolic changes in macrophages on atherosclerotic plaque progression and stability is not well understood and an area of intensive study. In this review, we will summarize and critically discuss recent developments in the field of macrophage metabolism in the context of atherosclerosis to guide future investigation in this area.
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Activated immune cells increase anabolism and rewire their metabolism towards enhanced glycolysis.
“Activated immune cells increase anabolism and rewire their metabolism towards enhanced glycolysis (Bories and Leitinger, 2017).”
From Overexpressing low‐density lipoprotein receptor reduces tau‐associated neurodegeneration in relation to apoE‐linked mechanisms (2021) · cites this paper as Bories and Leitinger, 2017
Proinflammatory M1 microglia show a profound metabolic change characterized by increased glucose uptake and a switch from oxidative phosphorylation to glycolysis even in normoxic conditions (Warburg effect).
“Proinflammatory “M1” microglia show a profound metabolic change characterized by increased glucose uptake and a switch from oxidative phosphorylation (OXPHOS) to glycolysis even in normoxic conditions (Warburg effect) (Bories and Leitinger, 2017).”
From Overexpressing low‐density lipoprotein receptor reduces tau‐associated neurodegeneration in relation to apoE‐linked mechanisms (2021) · cites this paper as Bories and Leitinger, 2017
Cites
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802987 · Cited by 7,397 · see citing works
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069 · see citing works
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989 · see citing works
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189 · see citing works
Succinate is an inflammatory signal that induces IL-1β through HIF-1α
Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., et al. (2013) · Nature · doi:10.1038/nature11986 · Cited by 4,176 · see citing works
Autophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506 · see citing works
Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., & Henson, P. M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1112 · Cited by 3,166 · see citing works
Macrophage-specific PPARγ controls alternative activation and improves insulin resistance
Odegaard, J. I., Ricardo-Gonzalez, R. R., Goforth, M. H., Morel, C. R., Subramanian, V., Mukundan, L., Eagle, A. R., Vats, D., Brombacher, F., Ferrante, A. W., et al. (2007) · Nature · doi:10.1038/nature05894 · Cited by 2,107 · see citing works
NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α
Rius, J., Guma, M., Schachtrup, C., Akassoglou, K., Zinkernagel, A. S., Nizet, V., Johnson, R. S., Haddad, G. G., & Karin, M. (2008) · Nature · doi:10.1038/nature06905 · Cited by 1,614 · see citing works
Palsson-McDermott, E. M., Curtis, A. M., Goel, G., Lauterbach, M. A. R., Sheedy, F. J., Gleeson, L. E., van den Bosch, M. W. M., Quinn, S. R., Domingo-Fernandez, R., Johnston, D. G. W., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2014.12.005 · Cited by 1,397 · see citing works
Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation
Vats, D., Mukundan, L., Odegaard, J. I., Zhang, L., Smith, K. L., Morel, C. R., Greaves, D. R., Murray, P. J., & Chawla, A. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.05.011 · Cited by 1,369 · see citing works
Everts, B., Amiel, E., Huang, S. C.-C., Smith, A. M., Chang, C.-H., Lam, W. Y., Redmann, V., Freitas, T. C., Blagih, J., van der Windt, G. J. W., et al. (2014) · Nature Immunology · doi:10.1038/ni.2833 · Cited by 1,064 · see citing works
Recent insights into the cellular biology of atherosclerosis
Tabas, I., García-Cardeña, G., & Owens, G. K. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201412052 · Cited by 1,016 · see citing works
MicroRNA-33 and the SREBP Host Genes Cooperate to Control Cholesterol Homeostasis
Najafi-Shoushtari, S. H., Kristo, F., Li, Y., Shioda, T., Cohen, D. E., Gerszten, R. E., & Näär, A. M. (2010) · Science · doi:10.1126/science.1189123 · Cited by 957 · see citing works
Clementi, E., Brown, G. C., Feelisch, M., & Moncada, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7631 · Cited by 863 · see citing works
Autophagy Regulates Cholesterol Efflux from Macrophage Foam Cells via Lysosomal Acid Lipase
Ouimet, M., Franklin, V., Mak, E., Liao, X., Tabas, I., & Marcel, Y. L. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.023 · Cited by 774 · see citing works
Kang, K., Reilly, S. M., Karabacak, V., Gangl, M. R., Fitzgerald, K., Hatano, B., & Lee, C.-H. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.04.002 · Cited by 699 · see citing works
miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling
Dávalos, A., Goedeke, L., Smibert, P., Ramírez, C. M., Warrier, N. P., Andreo, U., Cirera-Salinas, D., Rayner, K., Suresh, U., Pastor-Pareja, J. C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102281108 · Cited by 670 · see citing works
The Sedoheptulose Kinase CARKL Directs Macrophage Polarization through Control of Glucose Metabolism
Haschemi, A., Kosma, P., Gille, L., Evans, C. R., Burant, C. F., Starkl, P., Knapp, B., Haas, R., Schmid, J. A., Jandl, C., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.023 · Cited by 635 · see citing works
Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis
Schrijvers, D. M., De Meyer, G. R. Y., Kockx, M. M., Herman, A. G., & Martinet, W. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000166517.18801.a7 · Cited by 509 · see citing works
Ouimet, M., Ediriweera, H. N., Gundra, U. M., Sheedy, F. J., Ramkhelawon, B., Hutchison, S. B., Rinehold, K., van Solingen, C., Fullerton, M. D., Cecchini, K., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81676 · Cited by 394 · see citing works
Chinetti-Gbaguidi, G., Baron, M., Bouhlel, M. A., Vanhoutte, J., Copin, C., Sebti, Y., Derudas, B., Mayi, T., Bories, G., Tailleux, A., et al. (2011) · Circulation Research · doi:10.1161/circresaha.110.233775 · Cited by 387 · see citing works
Self-citationExpression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation*
Gerin, I., Clerbaux, L.-A., Haumont, O., Lanthier, N., Das, A. K., Burant, C. F., Leclercq, I. A., MacDougald, O. A., & Bommer, G. T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.152090 · Cited by 382 · see citing works
PPAR-δ senses and orchestrates clearance of apoptotic cells to promote tolerance
Mukundan, L., Odegaard, J. I., Morel, C. R., Heredia, J. E., Mwangi, J. W., Ricardo-Gonzalez, R. R., Goh, Y. P. S., Eagle, A. R., Dunn, S. E., Awakuni, J. U. H., et al. (2009) · Nature Medicine · doi:10.1038/nm.2048 · Cited by 368 · see citing works
Fujisaka, S., Usui, I., Ikutani, M., Aminuddin, A., Takikawa, A., Tsuneyama, K., Mahmood, A., Goda, N., Nagai, Y., Takatsu, K., et al. (2013) · Diabetologia · doi:10.1007/s00125-013-2885-1 · Cited by 239 · see citing works
Goff, D. C., Gerstein, H. C., Ginsberg, H. N., Cushman, W. C., Margolis, K. L., Byington, R. P., Buse, J. B., Genuth, S., Probstfield, J. L., & Simons-Morton, D. G. (2007) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2007.03.002 · Cited by 229 · see citing works
Risk Factors for Cardiovascular Disease in Type 1 Diabetes
The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group (2016) · Diabetes · doi:10.2337/db15-1517 · Cited by 209 · see citing works
Testing the role of myeloid cell glucose flux in inflammation and atherosclerosis
Nishizawa, T., Kanter, J. E., Kramer, F., Barnhart, S., Shen, X., Vivekanandan-Giri, A., Wall, V. Z., Kowitz, J., Devaraj, S., O’Brien, K. D., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.028 · Cited by 87 · see citing works
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Shi, Y., Andhey, P. S., Ising, C., Wang, K., Snipes, L. L., Boyer, K., Lawson, S., Yamada, K., Qin, W., Manis, M., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.05.034 · Cited by 135 · see citing works
Serum Metrnl is associated with the presence and severity of coronary artery disease
Liu, Z., Ji, H., Yao, M., Wang, L., Wang, Y., Zhou, P., Liu, Y., Zheng, X., He, H., Wang, L., et al. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13915 · Cited by 84 · see citing works
- Authors
- Bories, G. F. P., & Leitinger, N.
- Affiliations
- University of Virginia (US)
- Corresponding author
- Leitinger, Norbert
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2017-09-07
- Volume
- 591
- Issue
- 19
- Pages
- 3042-3060
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2744951299
- Cited by
- 145
- References
- 28
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 15 · 2023: 13 · 2022: 22 · 2021: 15 · 2020: 23 · 2019: 15 · 2018: 20 · 2017: 3
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- atherosclerosis, macrophage metabolism, macrophage polarization, plaque hemorrhage, oxidized phospholipids, lipid accumulation, inflammation resolution, plaque stability, macrophage heterogeneity, lipoprotein accumulation, redox regulation, glutathione
- MeSH terms
- Animals, Energy Metabolism, Humans, Macrophages, Models, Biological, Phenotype, Atherosclerosis
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