Pathophysiological relevance of macrophage subsets in atherogenesis

Thrombosis and Haemostasis

Volumn 117, Issue 1, 2017, Pages 7-18

  Liberale, Luca ^a   Dallegri, Franco ^a,b   Montecucco, Fabrizio ^a,b   Carbone, Federico ^a  

^a UNIVERSITY OF GENOA   (Italy)

^b UNIVERSITY OF GENOA   (Italy)

Author keywords

Atherosclerosis; Macrophage; Monocyte; Polarisation

Indexed keywords

BETA INTERFERON; CD14 ANTIGEN; CD16 ANTIGEN; DIPEPTIDYL CARBOXYPEPTIDASE; GAMMA INTERFERON; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYPOXIA INDUCIBLE FACTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON REGULATORY FACTOR 4; INTERLEUKIN 12; INTERLEUKIN 1BETA; INTERLEUKIN 6; LIVER X RECEPTOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MANNOSE RECEPTOR; MICRORNA; MICRORNA 155; REACTIVE OXYGEN METABOLITE; STAT6 PROTEIN; THROMBOCYTE FACTOR 4; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR;

ATHEROGENESIS; ATHEROSCLEROTIC PLAQUE; CARDIOVASCULAR DISEASE; CELL DIFFERENTIATION; CELL PROLIFERATION; GENE EXPRESSION; HISTONE METHYLATION; HUMAN; HYPERCHOLESTEROLEMIA; IMMUNOHISTOCHEMISTRY; MACROPHAGE; MICROENVIRONMENT; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOPHYSIOLOGY; PHENOTYPE; POLARIZATION AND DEPOLARIZATION; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; REVIEW; UPREGULATION; ANIMAL; ATHEROSCLEROSIS; MACROPHAGE ACTIVATION; METABOLISM; MONOCYTE; PATHOLOGY; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT;

ANIMALS; ATHEROSCLEROSIS; CELL DIFFERENTIATION; CELLULAR MICROENVIRONMENT; HUMANS; MACROPHAGE ACTIVATION; MACROPHAGES; MONOCYTES; PHENOTYPE; PLAQUE, ATHEROSCLEROTIC; SIGNAL TRANSDUCTION;

EID: 85007305130     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH16-08-0593     Document Type: Review

References (181)

1. Finn AV, et al. Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol 2010; 30: 1282-1292.
2. Montecucco F, et al. Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments. Eur Heart J 2016; 37: 1268-1283.
3. Leitinger N, Schulman IG. Phenotypic polarisation of macrophages in atherosclerosis. Arterioscler Thromb Vasc Biol 2013; 33: 1120-1126.
4. Robbins CS, et al. Extramedullary hematopoiesis generates Ly-6C(high) monocytes that infiltrate atherosclerotic lesions. Circulation 2012; 125: 364-374.
5. Robbins CS, et al. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat Med 2013; 19: 1166-1172.
6. Allahverdian S, et al. Contribution of intimal smooth muscle cells to cholesterol accumulation and macrophage-like cells in human atherosclerosis. Circulation 2014; 129: 1551-1559.
7. Feil S, et al. Transdifferentiation of vascular smooth muscle cells to macrophage- like cells during atherogenesis. Circ Res 2014; 115: 662-667.
8. Mantovani A, et al. Macrophage diversity and polarisation in atherosclerosis: a question of balance. Arterioscler Thromb Vasc Biol 2009; 29: 1419-1423.
9. Geissmann F, et al. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 2003; 19: 71-82.
10. Ziegler-Heitbrock L. Monocyte subsets in man and other species. Cell Immunol 2014; 289: 135-139.
11. Auffray C, et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 2007; 317: 666-670.
12. Swirski FK, et al. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest 2007; 117: 195-205.
13. Tacke F, et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 2007; 117: 185-194.
14. Potteaux S, et al. Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe-/- mice during disease regression. J Clin Invest 2011; 121: 2025-2036.
15. Al-Sharea A, et al. Native LDL promotes differentiation of human monocytes to macrophages with an inflammatory phenotype. Thromb Haemost 2016; 115: 762-772.
16. Williams HJ, et al. Macrophage differentiation and function in atherosclerosis: opportunities for therapeutic intervention? J Innate Immun 2012; 4: 498-508.
17. De Paoli F, et al. Macrophage phenotypes and their modulation in atherosclerosis. Circ J 2014; 78: 1775-1781.
18. Rojas J, et al. Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis. Scientifica 2015; 2015: 851252.
19. Weber C, et al. Role and analysis of monocyte subsets in cardiovascular disease. Joint consensus document of the European Society of Cardiology (ESC) Working Groups "Atherosclerosis & Vascular Biology" and "Thrombosis". Thromb Haemost 2016; 116: 626-637.
20. Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol 2007; 81: 584-592.
21. Cros J, et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 2010; 33: 375-386.
22. Huang ZS, Chiang BL. Correlation between serum lipid profiles and the ratio and count of the CD16+ monocyte subset in peripheral blood of apparently healthy adults. J Formos Med Assoc 2002; 101: 11-17.
23. Ingersoll MA, et al. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 2010; 115: e10-19.
24. Sternberg Z, et al. Flow cytometry and gene expression profiling of immune cells of the carotid plaque and peripheral blood. Atherosclerosis 2013; 229: 338-347.
25. Krausgruber T, et al. IRF5 promotes inflammatory macrophage polarisation and TH1-TH17 responses. Nat Immunol 2011; 12: 231-238.
26. Weiss M, et al. IRF5 is a specific marker of inflammatory macrophages in vivo. Mediators Inflamm 2013; 2013: 245804.
27. Bonizzi G, Karin M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 2004; 25: 280-288.
28. Vink A, et al. HIF-1 alpha expression is associated with an atheromatous inflammatory plaque phenotype and upregulated in activated macrophages. Atherosclerosis 2007; 195: e69-75.
29. Hutter R, et al. Macrophages transmit potent proangiogenic effects of oxLDL in vitro and in vivo involving HIF-1alpha activation: a novel aspect of angiogenesis in atherosclerosis. J Cardiovasc Transl Res 2013; 6: 558-569.
30. Chen CZ, et al. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004; 303: 83-86.
31. O’Connell RM, et al. MicroRNA function in myeloid biology. Blood 2011; 118: 2960-2969.
32. Ahlin F, et al. MicroRNAs as circulating biomarkers in acute coronary syndromes: A review. Vascul Pharmacol 2016; 81: 15-21.
33. Gao Y, et al. Functional regulatory roles of microRNAs in atherosclerosis. Clin Chim Acta 2016; 460: 164-171.
34. Wu XQ, et al. Emerging role of microRNAs in regulating macrophage activation and polarisation in immune response and inflammation. Immunology 2016; 148: 237-248.
35. Cai X, et al. Re-polarisation of tumor-associated macrophages to pro-inflammatory M1 macrophages by microRNA-155. J Mol Cell Biol 2012; 4: 341-343.
36. Zhang E, Wu Y. Dual effects of miR-155 on macrophages at different stages of atherosclerosis: LDL is the key? Med Hypotheses 2014; 83: 74-78.
37. Duewell P, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 2010; 464: 1357-1361.
38. Huber J, et al. Oxidised cholesteryl linoleates stimulate endothelial cells to bind monocytes via the extracellular signal-regulated kinase 1/2 pathway. Arterioscler Thromb Vasc Biol 2002; 22: 581-586.
39. Huang Z, et al. 7-ketocholesteryl-9-carboxynonanoate induced nuclear factorkappa B activation in J774A.1 macrophages. Life Sci 2010; 87: 651-657.
40. Seneviratne AN, et al. Low shear stress induces M1 macrophage polarisation in murine thin-cap atherosclerotic plaques. J Mol Cell Cardiol 2015; 89: 168-172.
41. Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003; 3: 23-35.
42. Satoh T, et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarisation and host responses against helminth infection. Nat Immunol 2010; 11: 936-944.
43. Junttila IS, et al. Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4Ralpha, IL-13Ralpha1, and gammac regulates relative cytokine sensitivity. J Exp Med 2008; 205: 2595-2608.
44. Odegaard JI, et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 2007; 447: 1116-1120.
45. Kang K, et al. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarisation and insulin sensitivity. Cell Metab 2008; 7: 485-495.
46. Takeda N, et al. Differential activation and antagonistic function of HIF-{alpha} isoforms in macrophages are essential for NO homeostasis. Genes Dev 2010; 24: 491-501.
47. Liao X, et al. Kruppel-like factor 4 regulates macrophage polarisation. J Clin Invest 2011; 121: 2736-2749.
48. Campbell L, et al. Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair. J Invest Dermatol 2014; 134: 2447-2457.
49. El Kasmi KC, et al. Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nat Immunol 2008; 9: 1399-1406.
50. Feig JE, et al. HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cells. Proc Natl Acad Sci USA 2011; 108: 7166-7171.
51. Sanson M, et al. HDL induces the expression of the M2 macrophage markers arginase 1 and Fizz-1 in a STAT6-dependent process. PLoS One 2013; 8: e74676.
52. Lovren F, et al. Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages. Am J Physiol Heart Circ Physiol 2010; 299: H656-663.
53. Miller AM, et al. Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res 2010; 107: 650-658.
54. Baitsch D, et al. Apolipoprotein E induces antiinflammatory phenotype in macrophages. Arterioscler Thromb Vasc Biol 2011; 31: 1160-1168.
55. Kohlstedt K, et al. Adipocyte-derived lipids increase angiotensin-converting enzyme (ACE) expression and modulate macrophage phenotype. Basic Res Cardiol 2011; 106: 205-215.
56. Ma LJ, et al. Angiotensin type 1 receptor modulates macrophage polarisation and renal injury in obesity. Am J Physiol Renal Physiol 2011; 300: F1203-1213.
57. Devaraj S, Jialal I. C-reactive protein polarizes human macrophages to an M1 phenotype and inhibits transformation to the M2 phenotype. Arterioscler Thromb Vasc Biol 2011; 31: 1397-1402.
58. Adamson S, Leitinger N. Phenotypic modulation of macrophages in response to plaque lipids. Curr Opin Lipidol 2011; 22: 335-342.
59. Sottero B, et al. Expression and synthesis of TGFbeta1 is induced in macrophages by 9-oxononanoyl cholesterol, a major cholesteryl ester oxidation product. Biofactors 2005; 24: 209-216.
60. Hughes JE, et al. Sphingosine-1-phosphate induces an antiinflammatory phenotype in macrophages. Circ Res 2008; 102: 950-958.
61. Titos E, et al. Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarisation toward an M2-like phenotype. J Immunol 2011; 187: 5408-5418.
62. McCarthy C, et al. IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis. FASEB J 2013; 27: 499-510.
63. Repa JJ, et al. Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science 2000; 289: 1524-1529.
64. Tall AR, et al. HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab 2008; 7: 365-375.
65. Joseph SB, et al. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci USA 2002; 99: 7604-7609.
66. Levin N, et al. Macrophage liver X receptor is required for antiatherogenic activity of LXR agonists. Arterioscler Thromb Vasc Biol 2005; 25: 135-142.
67. Pourcet B, et al. LXRalpha regulates macrophage arginase 1 through PU.1 and interferon regulatory factor 8. Circ Res 2011; 109: 492-501.
68. Dai Y, et al. Regulation of MSR-1 and CD36 in macrophages by LOX-1 mediated through PPAR-gamma. Biochem Biophys Res Commun 2013; 431: 496-500.
69. Yoon YS, et al. PPARgamma activation following apoptotic cell instillation promotes resolution of lung inflammation and fibrosis via regulation of efferocytosis and proresolving cytokines. Mucosal Immunol 2015; 8: 1031-1046.
70. Lee CG, et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). J Exp Med 2001; 194: 809-821.
71. Jetten N, et al. Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote angiogenesis in vivo. Angiogenesis 2014; 17: 109-118.
72. Edwards JP, et al. Biochemical and functional characterisation of three activated macrophage populations. J Leukoc Biol 2006; 80: 1298-1307.
73. Novak ML, Koh TJ. Macrophage phenotypes during tissue repair. J Leukoc Biol 2013; 93: 875-881.
74. White MJ, Gomer RH. Trypsin, Tryptase, and Thrombin Polarize Macrophages towards a Pro-Fibrotic M2a Phenotype. PLoS One 2015; 10: e0138748.
75. Ambarus CA, et al. Soluble immune complexes shift the TLR-induced cytokine production of distinct polarized human macrophage subsets towards IL-10. PLoS One 2012; 7: e35994.
76. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008; 8: 958-969.
77. Gerber JS, Mosser DM. Reversing lipopolysaccharide toxicity by ligating the macrophage Fc gamma receptors. J Immunol 2001; 166: 6861-6868.
78. Mantovani A, et al. The chemokine system in diverse forms of macrophage activation and polarisation. Trends Immunol 2004; 25: 677-686.
79. Ohlsson SM, et al. Serum from patients with systemic vasculitis induces alternatively activated macrophage M2c polarisation. Clin Immunol 2014; 152: 10-19.
80. Ferrante CJ, Leibovich SJ. Regulation of Macrophage Polarisation and Wound Healing. Adv Wound Care 2012; 1: 10-16.
81. Pinhal-Enfield G, et al. An angiogenic switch in macrophages involving synergy between Toll-like receptors 2, 4, 7, and 9 and adenosine A(2A) receptors. Am J Pathol 2003; 163: 711-721.
82. Grinberg S, et al. Suppression of PLCbeta2 by endotoxin plays a role in the adenosine A(2A) receptor-mediated switch of macrophages from an inflammatory to an angiogenic phenotype. Am J Pathol 2009; 175: 2439-2453.
83. Ferrante CJ, et al. The adenosine-dependent angiogenic switch of macrophages to an M2-like phenotype is independent of interleukin-4 receptor alpha (IL-4Ralpha) signalling. Inflammation 2013; 36: 921-931.
84. Wu WK, et al. IL-10 regulation of macrophage VEGF production is dependent on macrophage polarisation and hypoxia. Immunobiology 2010; 215: 796-803.
85. Kadl A, et al. Identification of a novel macrophage phenotype that develops in response to atherogenic phospholipids via Nrf2. Circ Res 2010; 107: 737-746.
86. Marques L, et al. Iron gene expression profile in atherogenic Mox macrophages. Biochim Biophys Acta 2016; 1862: 1137-1146.
87. Kadl A, et al. Oxidised phospholipid-induced inflammation is mediated by Tolllike receptor 2. Free Radic Biol Med 2011; 51: 1903-1909.
88. Kolodgie FD, et al. Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med 2003; 349: 2316-2325.
89. Kockx MM, et al. Phagocytosis and macrophage activation associated with hemorrhagic microvessels in human atherosclerosis. Arterioscler Thromb Vasc Biol 2003; 23: 440-446.
90. Sindrilaru A, et al. An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J Clin Invest 2011; 121: 985-997.
91. Boyle JJ, et al. Coronary intraplaque hemorrhage evokes a novel atheroprotective macrophage phenotype. Am J Pathol 2009; 174: 1097-1108.
92. Boyle JJ, et al. Activating transcription factor 1 directs Mhem atheroprotective macrophages through coordinated iron handling and foam cell protection. Circ Res 2012; 110: 20-33.
93. Boyle JJ, et al. Heme induces heme oxygenase 1 via Nrf2: role in the homeostatic macrophage response to intraplaque hemorrhage. Arterioscler Thromb Vasc Biol 2011; 31: 2685-2691.
94. Kristiansen M, et al. Identification of the haemoglobin scavenger receptor. Nature 2001; 409: 198-201.
95. Madsen M, Graversen JH, Moestrup SK. Haptoglobin and CD163: captor and receptor gating hemoglobin to macrophage lysosomes. Redox Rep 2001; 6: 386-388.
96. Finn AV, et al. Hemoglobin directs macrophage differentiation and prevents foam cell formation in human atherosclerotic plaques. J Am Coll Cardiol 2012; 59: 166-177.
97. Gleissner CA, et al. CXC chemokine ligand 4 induces a unique transcriptome in monocyte-derived macrophages. J Immunol 2010; 184: 4810-4818.
98. Gleissner CA, et al. CXCL4 downregulates the atheroprotective hemoglobin receptor CD163 in human macrophages. Circ Res 2010; 106: 203-211.
99. Erbel C, et al. CXCL4-induced plaque macrophages can be specifically identified by co-expression of MMP7+S100A8+ in vitro and in vivo. Innate Immun 2015; 21: 255-265.
100. Stoger JL, et al. Distribution of macrophage polarisation markers in human atherosclerosis. Atherosclerosis 2012; 225: 461-468.
101. Chinetti-Gbaguidi G, et al. Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARgamma and LXRalpha pathways. Circ Res 2011; 108: 985-995.
102. Cho KY, et al. The phenotype of infiltrating macrophages influences arteriosclerotic plaque vulnerability in the carotid artery. J Stroke Cerebrovasc Dis 2013; 22: 910-918.
103. Lee CW, et al. Macrophage heterogeneity of culprit coronary plaques in patients with acute myocardial infarction or stable angina. Am J Clin Pathol 2013; 139: 317-322.
104. Medbury HJ, et al. Differing association of macrophage subsets with atherosclerotic plaque stability. Int Angiol 2013; 32: 74-84.
105. Howard DP, et al. Symptomatic carotid atherosclerotic disease: correlations between plaque composition and ipsilateral stroke risk. Stroke 2015; 46: 182-189.
106. Erbel C, et al. Prevalence of M4 macrophages within human coronary atherosclerotic plaques is associated with features of plaque instability. Int J Cardiol 2015; 186: 219-225.
107. Carbone F, et al. Vitamin D receptor is expressed within human carotid plaques and correlates with pro-inflammatory M1 macrophages. Vascul Pharmacol 2016; Epub ahead of print.
108. Tawakol A, et al. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol 2006; 48: 1818-1824.
109. Gaemperli O, et al. Imaging intraplaque inflammation in carotid atherosclerosis with 11C-PK11195 positron emission tomography/computed tomography. Eur Heart J 2012; 33: 1902-1910.
110. Degnan AJ, et al. Evaluation of ultrasmall superparamagnetic iron oxide-enhanced MRI of carotid atherosclerosis to assess risk of cerebrovascular and cardiovascular events: follow-up of the ATHEROMA trial. Cerebrovasc Dis 2012; 34: 169-173.
111. Saito H, et al. Validity of dual MRI and F-FDG PET imaging in predicting vulnerable and inflamed carotid plaque. Cerebrovasc Dis 2013; 35: 370-377.
112. Fukuda K, et al. Relationship between carotid artery remodeling and plaque vulnerability with T1-weighted magnetic resonance imaging. J Stroke Cerebrovasc Dis 2014; 23: 1462-1470.
113. Khallou-Laschet J, et al. Macrophage plasticity in experimental atherosclerosis. PLoS One 2010; 5: e8852.
114. Lee PP, et al. The many faces of Artemis-deficient combined immunodeficiency - Two patients with DCLRE1C mutations and a systematic literature review of genotype-phenotype correlation. Clin Immunol 2013; 149: 464-474.
115. Mukhopadhyay S, et al. Formation of distinct chromatin conformation signatures epigenetically regulate macrophage activation. Int Immunopharmacol 2014; 18: 7-11.
116. Eames HL, et al. KAP1/TRIM28: an inhibitor of IRF5 function in inflammatory macrophages. Immunobiology 2012; 217: 1315-1324.
117. Van den Bossche J, et al. Inhibiting epigenetic enzymes to improve atherogenic macrophage functions. Biochem Biophys Res Commun 2014; 455: 396-402.
118. Austenaa L, et al. The histone methyltransferase Wbp7 controls macrophage function through GPI glycolipid anchor synthesis. Immunity 2012; 36: 572-585.
119. Stender JD, et al. Control of proinflammatory gene programs by regulated trimethylation and demethylation of histone H4K20. Mol Cell 2012; 48: 28-38.
120. Kapellos TS, Iqbal AJ. Epigenetic Control of Macrophage Polarisation and Soluble Mediator Gene Expression during Inflammation. Mediators Inflamm 2016; 2016: 6591703.
121. Greissel A, et al. Histone acetylation and methylation significantly change with severity of atherosclerosis in human carotid plaques. Cardiovasc Pathol 2016; 25: 79-86.
122. Tabas I, Bornfeldt KE. Macrophage Phenotype and Function in Different Stages of Atherosclerosis. Circ Res 2016; 118: 653-667.
123. Fadini GP, et al. Pro-inflammatory monocyte-macrophage polarisation imbalance in human hypercholesterolemia and atherosclerosis. Atherosclerosis 2014; 237: 805-808.
124. Escate R, et al. LDL accelerates monocyte to macrophage differentiation: Effects on adhesion and anoikis. Atherosclerosis 2016; 246: 177-186.
125. Cho HJ, et al. Induction of dendritic cell-like phenotype in macrophages during foam cell formation. Physiol Genomics 2007; 29: 149-160.
126. Park YM, et al. CD36 modulates migration of mouse and human macrophages in response to oxidised LDL and may contribute to macrophage trapping in the arterial intima. J Clin Invest 2009; 119: 136-145.
127. Sheedy FJ, et al. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol 2010; 11: 141-147.
128. Manning-Tobin JJ, et al. Loss of SR-A and CD36 activity reduces atherosclerotic lesion complexity without abrogating foam cell formation in hyperlipidemic mice. Arterioscler Thromb Vasc Biol 2009; 29: 19-26.
129. Spann NJ, et al. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 2012; 151: 138-152.
130. Sarov-Blat L, et al. Predominance of a proinflammatory phenotype in monocyte- derived macrophages from subjects with low plasma HDL-cholesterol. Arterioscler Thromb Vasc Biol 2007; 27: 1115-1122.
131. Bouhlel MA, et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab 2007; 6: 137-143.
132. van der Meij E, et al. A clinical evaluation of statin pleiotropy: statins selectively and dose-dependently reduce vascular inflammation. PLoS One 2013; 8: e53882.
133. Hirata Y, et al. Coronary atherosclerosis is associated with macrophage polarisation in epicardial adipose tissue. J Am Coll Cardiol 2011; 58: 248-255.
134. Fadini GP, et al. Monocyte-macrophage polarisation balance in pre-diabetic individuals. Acta Diabetol 2013; 50: 977-982.
135. Roma-Lavisse C, et al. M1 and M2 macrophage proteolytic and angiogenic profile analysis in atherosclerotic patients reveals a distinctive profile in type 2 diabetes. Diab Vasc Dis Res 2015; 12: 279-289.
136. Torres-Castro I, et al. Human monocytes and macrophages undergo M1-type inflammatory polarisation in response to high levels of glucose. Immunol Lett 2016; 176: 81-89.
137. Marsch E, et al. Reversal of hypoxia in murine atherosclerosis prevents necrotic core expansion by enhancing efferocytosis. Arterioscler Thromb Vasc Biol 2014; 34: 2545-2553.
138. Sluimer JC, et al. Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis. J Am Coll Cardiol 2008; 51: 1258-1265.
139. Tawakol A, et al. Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography. J Nucl Cardiol 2005; 12: 294-301.
140. Tahara N, et al. Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 2006; 48: 1825-1831.
141. Lee SJ, et al. Reversal of vascular 18F-FDG uptake with plasma high-density lipoprotein elevation by atherogenic risk reduction. J Nucl Med 2008; 49: 1277-1282.
142. Folco EJ, et al. Hypoxia but not inflammation augments glucose uptake in human macrophages: Implications for imaging atherosclerosis with 18fluorinelabeled 2-deoxy-D-glucose positron emission tomography. J Am Coll Cardiol 2011; 58: 603-614.
143. Matter CM, et al. 18F-choline images murine atherosclerotic plaques ex vivo. Arterioscler Thromb Vasc Biol 2006; 26: 584-589.
144. Davies JR, et al. FDG-PET can distinguish inflamed from non-inflamed plaque in an animal model of atherosclerosis. Int J Cardiovasc Imaging 2010; 26: 41-48.
145. Lamare F, et al. Detection and quantification of large-vessel inflammation with 11C-(R)-PK11195 PET/CT. J Nucl Med 2011; 52: 33-39.
146. Fujimura Y, et al. Increased peripheral benzodiazepine receptors in arterial plaque of patients with atherosclerosis: an autoradiographic study with [(3)H]PK 11195. Atherosclerosis 2008; 201: 108-111.
147. Gerretsen SC, et al. Visualisation of coronary wall atherosclerosis in asymptomatic subjects and patients with coronary artery disease using magnetic resonance imaging. PLoS One 2010; 5: pii: e12998.
148. Kerwin WS, et al. Inflammation in carotid atherosclerotic plaque: a dynamic contrast-enhanced MR imaging study. Radiology 2006; 241: 459-468.
149. Chan JM, et al. Imaging of the vulnerable carotid plaque: biological targeting of inflammation in atherosclerosis using iron oxide particles and MRI. Eur J Vasc Endovasc Surg 2014; 47: 462-469.
150. Trivedi RA, et al. Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages. Arterioscler Thromb Vasc Biol 2006; 26: 1601-1606.
151. Jaffer FA, et al. Cellular imaging of inflammation in atherosclerosis using magnetofluorescent nanomaterials. Mol Imaging 2006; 5: 85-92.
152. Metz S. Biomarkers for plaque vulnerability. Int J Cardiovasc Imaging 2011; 27: 901-912.
153. Mani V, et al. Feasibility of in vivo identification of endogenous ferritin with positive contrast MRI in rabbit carotid crush injury using GRASP. Magn Reson Med 2006; 56: 1096-1106.
154. Makowski MR, et al. Noninvasive assessment of atherosclerotic plaque progression in ApoE-/- mice using susceptibility gradient mapping. Circ Cardiovasc Imaging 2011; 4: 295-303.
155. Dong Y, et al. Polymer-Lipid Hybrid Theranostic Nanoparticles Co-Delivering Ultrasmall Superparamagnetic Iron Oxide and Paclitaxel for Targeted Magnetic Resonance Imaging and Therapy in Atherosclerotic Plaque. J Biomed Nanotechnol 2016; 12: 1245-1257.
156. Segers FM, et al. Scavenger receptor-AI-targeted iron oxide nanoparticles for in vivo MRI detection of atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2013; 33: 1812-1819.
157. Sha T, et al. Experimental study of USPIO-enhanced MRI in the detection of atherosclerotic plaque and the intervention of atorvastatin. Exp Ther Med 2016; 12: 141-146.
158. Tang TY, et al. The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. J Am Coll Cardiol 2009; 53: 2039-2050.
159. Weissleder R, et al. Imaging macrophages with nanoparticles. Nat Mater 2014; 13: 125-138.
160. Nahrendorf M, et al. Hybrid in vivo FMT-CT imaging of protease activity in atherosclerosis with customized nanosensors. Arterioscler Thromb Vasc Biol 2009; 29: 1444-1451.
161. Lipinski MJ, et al. Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterisation of human atherosclerosis. JACC Cardiovasc Imaging 2009; 2: 637-647.
162. Briley-Saebo KC, et al. Targeted iron oxide particles for in vivo magnetic resonance detection of atherosclerotic lesions with antibodies directed to oxidationspecific epitopes. J Am Coll Cardiol 2011; 57: 337-347.
163. Amirbekian V, et al. Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI. Proc Natl Acad Sci USA 2007; 104: 961-966.
164. Majmudar MD, et al. Polymeric nanoparticle PET/MR imaging allows macrophage detection in atherosclerotic plaques. Circ Res 2013; 112: 755-761.
165. Murray PJ, et al. Macrophage activation and polarisation: nomenclature and experimental guidelines. Immunity 2014; 41: 14-20.
166. Novoselov VV, et al. Study of the activated macrophage transcriptome. Exp Mol Pathol 2015; 99: 575-580.
167. Gosselin D, et al. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 2014; 159: 1327-1340.
168. Lavin Y, et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 2014; 159: 1312-1326.
169. Xue J, et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 2014; 40: 274-288.
170. Schultze JL. Transcriptional programming of human macrophages: on the way to systems immunology. J Mol Med 2015; 93: 589-597.
171. Calfon MA, et al. In vivo near infrared fluorescence (NIRF) intravascular molecular imaging of inflammatory plaque, a multimodal approach to imaging of atherosclerosis. J Vis Exp 2011; 54: pii: 2257.
172. Zhou M, et al. Fluorescence Imaging of Inflammation in Live Animals. Methods Mol Biol 2016; 1444: 45-54.
173. Shan L. Near-infrared fluorescence 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR)-labeled macrophages for cell imaging. In: Molecular Imaging and Contrast Agent Database (MICAD) 2004.
174. McCarthy JR, et al. A light-activated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis. Small 2010; 6: 2041-2049.
175. Shon SM, et al. Photodynamic therapy using a protease-mediated theranostic agent reduces cathepsin-B activity in mouse atheromata in vivo. Arterioscler Thromb Vasc Biol 2013; 33: 1360-1365.
176. Qin J, et al. Gold nanorods as a theranostic platform for in vitro and in vivo imaging and photothermal therapy of inflammatory macrophages. Nanoscale 2015; 7: 13991-14001.
177. Kim S, et al. Intracoronary dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular imaging with a clinical dose of indocyanine green for the assessment of high-risk plaques and stent-associated inflammation in a beating coronary artery. Eur Heart J 2016; Epub ahead of print.
178. Gomes Quindere AL, et al. Treatment with sulphated galactan inhibits macrophage chemotaxis and reduces intraplaque macrophage content in atherosclerotic mice. Vascul Pharmacol 2015; 71: 84-92.
179. Riek AE, et al. Vitamin D suppression of endoplasmic reticulum stress promotes an antiatherogenic monocyte/macrophage phenotype in type 2 diabetic patients. J Biol Chem 2012; 287: 38482-38494.
180. Riek AE, et al. 1,25(OH)2 vitamin D suppresses macrophage migration and reverses atherogenic cholesterol metabolism in type 2 diabetic patients. J Steroid Biochem Mol Biol 2013; 136: 309-312.
181. Yin K, et al. Vitamin D Protects Against Atherosclerosis via Regulation of Cholesterol Efflux and Macrophage Polarisation in Hypercholesterolemic Swine. Arterioscler Thromb Vasc Biol 2015; 35: 2432-2442.