Macrophages in Atherosclerosis: a Dynamic Balance

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2013 Sep 3

PMID 23995626

Citations 1138

Authors

Kathryn J Moore

Frederick J Sheedy

Edward A Fisher

Affiliations

Soon will be listed here.

Abstract

Atherosclerosis is a chronic inflammatory disease that arises from an imbalance in lipid metabolism and a maladaptive immune response driven by the accumulation of cholesterol-laden macrophages in the artery wall. Through the analysis of the progression and regression of atherosclerosis in animal models, there is a growing understanding that the balance of macrophages in the plaque is dynamic and that both macrophage numbers and the inflammatory phenotype influence plaque fate. In this Review, we summarize recently identified pro- and anti-inflammatory pathways that link lipid and inflammation biology with the retention of macrophages in plaques, as well as factors that have the potential to promote their egress from these sites.

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References

Saitoh T, Fujita N, Jang M, Uematsu S, Yang B, Satoh T . Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008; 456(7219):264-8. DOI: 10.1038/nature07383. View

Kunjathoor V, Febbraio M, Podrez E, Moore K, Andersson L, Koehn S . Scavenger receptors class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem. 2002; 277(51):49982-8. DOI: 10.1074/jbc.M209649200. View

Kugiyama K, Ota Y, Takazoe K, Moriyama Y, Kawano H, Miyao Y . Circulating levels of secretory type II phospholipase A(2) predict coronary events in patients with coronary artery disease. Circulation. 1999; 100(12):1280-4. DOI: 10.1161/01.cir.100.12.1280. View

Rekhter M, Staschke K, Estridge T, Rutherford P, Jackson N, Gifford-Moore D . Genetic ablation of IRAK4 kinase activity inhibits vascular lesion formation. Biochem Biophys Res Commun. 2008; 367(3):642-8. DOI: 10.1016/j.bbrc.2007.12.186. View

Leuschner F, Dutta P, Gorbatov R, Novobrantseva T, Donahoe J, Courties G . Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat Biotechnol. 2011; 29(11):1005-10. PMC: 3212614. DOI: 10.1038/nbt.1989. View

Chao L, Soto E, Hong C, Ito A, Pei L, Chawla A . Bone marrow NR4A expression is not a dominant factor in the development of atherosclerosis or macrophage polarization in mice. J Lipid Res. 2013; 54(3):806-815. PMC: 3617954. DOI: 10.1194/jlr.M034157. View

Gerrity R, Naito H . Lipid clearance from fatty streak lesions by foam cell migration. Artery. 1980; 8(3):215-9. View

Hornung V, Bauernfeind F, Halle A, Samstad E, Kono H, Rock K . Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008; 9(8):847-56. PMC: 2834784. DOI: 10.1038/ni.1631. View

Zhang M, Yao B, Yang S, Jiang L, Wang S, Fan X . CSF-1 signaling mediates recovery from acute kidney injury. J Clin Invest. 2012; 122(12):4519-32. PMC: 3533529. DOI: 10.1172/JCI60363. View

10.

Weber C, Noels H . Atherosclerosis: current pathogenesis and therapeutic options. Nat Med. 2011; 17(11):1410-22. DOI: 10.1038/nm.2538. View

11.

van Gils J, Ramkhelawon B, Fernandes L, Stewart M, Guo L, Seibert T . Endothelial expression of guidance cues in vessel wall homeostasis dysregulation under proatherosclerotic conditions. Arterioscler Thromb Vasc Biol. 2013; 33(5):911-9. PMC: 3647028. DOI: 10.1161/ATVBAHA.112.301155. View

12.

Serbina N, Pamer E . Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol. 2006; 7(3):311-7. DOI: 10.1038/ni1309. View

13.

Oorni K, Kovanen P . Lipoprotein modification by secretory phospholipase A(2) enzymes contributes to the initiation and progression of atherosclerosis. Curr Opin Lipidol. 2009; 20(5):421-7. DOI: 10.1097/MOL.0b013e32832fa14d. View

14.

Tardif J . Antioxidants: the good, the bad and the ugly. Can J Cardiol. 2006; 22 Suppl B:61B-65B. PMC: 2780837. DOI: 10.1016/s0828-282x(06)70988-6. View

15.

Freigang S, Ampenberger F, Spohn G, Heer S, Shamshiev A, Kisielow J . Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis. Eur J Immunol. 2011; 41(7):2040-51. DOI: 10.1002/eji.201041316. View

16.

Stewart C, Stuart L, Wilkinson K, van Gils J, Deng J, Halle A . CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2009; 11(2):155-61. PMC: 2809046. DOI: 10.1038/ni.1836. View

17.

Kadl A, Meher A, Sharma P, Lee M, Doran A, Johnstone S . Identification of a novel macrophage phenotype that develops in response to atherogenic phospholipids via Nrf2. Circ Res. 2010; 107(6):737-46. PMC: 2941538. DOI: 10.1161/CIRCRESAHA.109.215715. View

18.

Yvan-Charvet L, Wang N, Tall A . Role of HDL, ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses. Arterioscler Thromb Vasc Biol. 2009; 30(2):139-43. PMC: 2812788. DOI: 10.1161/ATVBAHA.108.179283. View

19.

Wanschel A, Seibert T, Hewing B, Ramkhelawon B, Ray T, van Gils J . Neuroimmune guidance cue Semaphorin 3E is expressed in atherosclerotic plaques and regulates macrophage retention. Arterioscler Thromb Vasc Biol. 2013; 33(5):886-93. PMC: 3647027. DOI: 10.1161/ATVBAHA.112.300941. View

20.

Randolph G . Emigration of monocyte-derived cells to lymph nodes during resolution of inflammation and its failure in atherosclerosis. Curr Opin Lipidol. 2008; 19(5):462-8. PMC: 2652166. DOI: 10.1097/MOL.0b013e32830d5f09. View