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Current Atherosclerosis Reports

Published in:

01-03-2018 | Evidence-Based Medicine (L. Roever, Section Editor)

The Interplay of Lipids, Lipoproteins, and Immunity in Atherosclerosis

Authors: Angela Pirillo, Fabrizia Bonacina, Giuseppe Danilo Norata, Alberico Luigi Catapano

Published in: Current Atherosclerosis Reports | Issue 3/2018

Abstract

Purpose of Review

Atherosclerosis is an inflammatory disorder of the arterial wall, in which several players contribute to the onset and progression of the disease. Besides the well-established role of lipids, specifically cholesterol, and immune cell activation, new insights on the molecular mechanisms underlying the atherogenic process have emerged.

Recent Findings

Meta-inflammation, a condition of low-grade immune response caused by metabolic dysregulation, immunological memory of innate immune cells (referred to as “trained immunity”), cholesterol homeostasis in dendritic cells, and immunometabolism, i.e., the interplay between immunological and metabolic processes, have all emerged as new actors during atherogenesis. These observations reinforced the interest in directly targeting inflammation to reduce cardiovascular disease.

Summary

The novel acquisitions in pathophysiology of atherosclerosis reinforce the tight link between lipids, inflammation, and immune response, and support the benefit of targeting LDL-C as well as inflammation to decrease the CVD burden. How this will translate into the clinic will depend on the balance between costs (monoclonal antibodies either to PCSK9 or to IL-1ß), side effects (increased incidence of death due to infections for anti-IL-1ß antibody), and the benefits for patients at high CVD risk.

Tabas I, Lichtman AH. Monocyte-macrophages and T cells in atherosclerosis. Immunity. 2017;47(4):621–34. https://doi.org/10.1016/j.immuni.2017.09.008.CrossRefPubMed

Lemaire-Ewing S, Lagrost L, Neel D. Lipid rafts: a signalling platform linking lipoprotein metabolism to atherogenesis. Atherosclerosis. 2012;221(2):303–10.CrossRefPubMed

Catapano AL, Pirillo A, Bonacina F, Norata GD. HDL in innate and adaptive immunity. Cardiovasc Res. 2014;103(3):372–83. https://doi.org/10.1093/cvr/cvu150.CrossRefPubMed

Norata GD, Pirillo A, Ammirati E, Catapano AL. Emerging role of high density lipoproteins as a player in the immune system. Atherosclerosis. 2011;220(1):11–21. https://doi.org/10.1016/j.atherosclerosis.2011.06.045.CrossRefPubMed

Norata GD, Pirillo A, Catapano AL. HDLs, immunity, and atherosclerosis. Curr Opin Lipidol. 2011;22(5):410–6.CrossRefPubMed

Varshney P, Yadav V, Saini N. Lipid rafts in immune signalling: current progress and future perspective. Immunology. 2016;149(1):13–24.CrossRefPubMedPubMedCentral

Simons K, Gerl MJ. Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol. 2010;11(10):688–99. https://doi.org/10.1038/nrm2977.CrossRefPubMed

Jury EC, Flores-Borja F, Kalsi HS, et al. Abnormal CTLA-4 function in T cells from patients with systemic lupus erythematosus. Eur J Immunol. 2010;40(2):569–78.CrossRefPubMed

Eren E, Yates J, Cwynarski K, et al. Location of major histocompatibility complex class II molecules in rafts on dendritic cells enhances the efficiency of T-cell activation and proliferation. Scand J Immunol. 2006;63(1):7–16.CrossRefPubMed

10.

Anderson HA, Hiltbold EM, Roche PA. Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation. Nat Immunol. 2000;1(2):156–62. https://doi.org/10.1038/77842.CrossRefPubMed

11.

Zhu X, Owen JS, Wilson MD, Li H, Griffiths GL, Thomas MJ, et al. Macrophage ABCA1 reduces MyD88-dependent toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol. J Lipid Res. 2010;51(11):3196–206. https://doi.org/10.1194/jlr.M006486.CrossRefPubMedPubMedCentral

12.

Ito A, Hong C, Oka K, et al. Cholesterol accumulation in CD11c+ immune cells is a causal and targetable factor in autoimmune disease. Immunity. 2016;45(6):1311–26.CrossRefPubMedPubMedCentral

13.

Foster GA, Xu L, Chidambaram AA, Soderberg SR, Armstrong EJ, Wu H, et al. CD11c/CD18 signals very late antigen-4 activation to initiate foamy monocyte recruitment during the onset of hypercholesterolemia. J Immunol. 2015;195(11):5380–92. https://doi.org/10.4049/jimmunol.1501077.CrossRefPubMedPubMedCentral

14.

Wu H, Gower RM, Wang H, Perrard XYD, Ma R, Bullard DC, et al. Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia. Circulation. 2009;119(20):2708–17. https://doi.org/10.1161/CIRCULATIONAHA.108.823740.CrossRefPubMedPubMedCentral

15.

Xu L, Dai Perrard X, Perrard JL, Yang D, Xiao X, Teng BB, et al. Foamy monocytes form early and contribute to nascent atherosclerosis in mice with hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2015;35(8):1787–97. https://doi.org/10.1161/ATVBAHA.115.305609.CrossRefPubMedPubMedCentral

16.

Khan IM, Pokharel Y, Dadu RT, et al. Postprandial monocyte activation in individuals with metabolic syndrome. J Clin Endocrinol Metab. 2016;101(11):4195–204.CrossRefPubMedPubMedCentral

17.

Maxfield FR, Tabas I. Role of cholesterol and lipid organization in disease. Nature. 2005;438(7068):612–21. https://doi.org/10.1038/nature04399.CrossRefPubMed

18.

Plakkal Ayyappan J, Paul A, Goo YH. Lipid droplet-associated proteins in atherosclerosis (review). Mol Med Rep. 2016;13(6):4527–34.CrossRefPubMed

19.

Netea MG, Joosten LA, Latz E, et al. Trained immunity: a program of innate immune memory in health and disease. Science. 2016;352(6284):aaf1098. https://doi.org/10.1126/science.aaf1098.CrossRefPubMedPubMedCentral

20.

Christ A, Bekkering S, Latz E, Riksen NP. Long-term activation of the innate immune system in atherosclerosis. Semin Immunol. 2016;28(4):384–93. https://doi.org/10.1016/j.smim.2016.04.004.CrossRefPubMed

21.

Pothineni NVK, Subramany S, Kuriakose K, et al. Infections, atherosclerosis, and coronary heart disease. Eur Heart J. 2017;38(43):3195–201.CrossRefPubMed

22.

Bekkering S, Quintin J, Joosten LA, van der Meer JW, Netea MG, Riksen NP. Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arterioscler Thromb Vasc Biol. 2014;34(8):1731–8. https://doi.org/10.1161/ATVBAHA.114.303887.CrossRefPubMed

23.

van der Valk FM, Bekkering S, Kroon J, et al. Oxidized phospholipids on lipoprotein(a) elicit arterial wall inflammation and an inflammatory monocyte response in humans. Circulation. 2016;134(8):611–24.CrossRefPubMedPubMedCentral

24.

van der Veen JN, Kruit JK, Havinga R, Baller JFW, Chimini G, Lestavel S, et al. Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1. J Lipid Res. 2005;46(3):526–34. https://doi.org/10.1194/jlr.M400400-JLR200.CrossRefPubMed

25.

Janoudi A, Shamoun FE, Kalavakunta JK, Abela GS. Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque. Eur Heart J. 2016;37(25):1959–67. https://doi.org/10.1093/eurheartj/ehv653.CrossRefPubMed

26.

Samstad EO, Niyonzima N, Nymo S, et al. Cholesterol crystals induce complement-dependent inflammasome activation and cytokine release. J Immunol. 2014;192(6):2837–45.CrossRefPubMedPubMedCentral

27.

Abela GS, Kalavakunta JK, Janoudi A, Leffler D, Dhar G, Salehi N, et al. Frequency of cholesterol crystals in culprit coronary artery aspirate during acute myocardial infarction and their relation to inflammation and myocardial injury. Am J Cardiol. 2017;120(10):1699–707. https://doi.org/10.1016/j.amjcard.2017.07.075.CrossRefPubMed

28.

Mason RP, Jacob RF. Membrane microdomains and vascular biology: emerging role in atherogenesis. Circulation. 2003;107(17):2270–3. https://doi.org/10.1161/01.CIR.0000062607.02451.B6.CrossRefPubMed

29.

Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002;10(2):417–26.CrossRefPubMed

30.

Karasawa T, Takahashi M. Role of NLRP3 inflammasomes in atherosclerosis. J Atheroscler Thromb. 2017;24(5):443–51. https://doi.org/10.5551/jat.RV17001.CrossRefPubMedPubMedCentral

31.

Duewell P, Kono H, Rayner KJ, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293):1357–61.CrossRefPubMedPubMedCentral

32.

Menu P, Pellegrin M, Aubert JF, Bouzourene K, Tardivel A, Mazzolai L, et al. Atherosclerosis in ApoE-deficient mice progresses independently of the NLRP3 inflammasome. Cell Death Dis. 2011;2(3):e137. https://doi.org/10.1038/cddis.2011.18.CrossRefPubMedPubMedCentral

33.

Sheedy FJ, Grebe A, Rayner KJ, et al. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat Immunol. 2013;14(8):812–20.CrossRefPubMedPubMedCentral

34.

Hendrikx T, Jeurissen ML, van Gorp PJ, et al. Bone marrow-specific caspase-1/11 deficiency inhibits atherosclerosis development in Ldlr(-/-) mice. FEBS J. 2015;282(12):2327–38. https://doi.org/10.1111/febs.13279.CrossRefPubMed

35.

Freigang S, Ampenberger F, Weiss A, et al. Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1alpha and sterile vascular inflammation in atherosclerosis. Nat Immunol. 2013;14(10):1045–53.CrossRefPubMed

36.

Tan HW, Liu X, Bi XP, et al. IL-18 overexpression promotes vascular inflammation and remodeling in a rat model of metabolic syndrome. Atherosclerosis. 2010;208(2):350–7.CrossRefPubMed

37.

de Nooijer R, von der Thusen JH, Verkleij CJ, et al. Overexpression of IL-18 decreases intimal collagen content and promotes a vulnerable plaque phenotype in apolipoprotein-E-deficient mice. Arterioscler Thromb Vasc Biol. 2004;24(12):2313–9. https://doi.org/10.1161/01.ATV.0000147126.99529.0a.CrossRefPubMed

38.

Kirii H, Niwa T, Yamada Y, et al. Lack of interleukin-1beta decreases the severity of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 2003;23(4):656–60.CrossRefPubMed

39.

Usui F, Shirasuna K, Kimura H, et al. Critical role of caspase-1 in vascular inflammation and development of atherosclerosis in Western diet-fed apolipoprotein E-deficient mice. Biochem Biophys Res Commun. 2012;425(2):162–8.CrossRefPubMed

40.

Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177–85. https://doi.org/10.1038/nature21363.CrossRefPubMed

41.

Norata GD, Caligiuri G, Chavakis T, et al. The cellular and molecular basis of translational immunometabolism. Immunity. 2015;43(3):421–34.CrossRefPubMed

42.

Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2010;11(2):136–40.CrossRefPubMed

43.

Masters SL, Latz E, O’Neill LA. The inflammasome in atherosclerosis and type 2 diabetes. Sci Transl Med. 2011;3(81):81ps17. https://doi.org/10.1126/scitranslmed.3001902.CrossRefPubMed

44.

Wen H, Gris D, Lei Y, et al. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol. 2011;12(5):408–15.CrossRefPubMedPubMedCentral

45.

Murphy AJ, Akhtari M, Tolani S, et al. ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice. J Clin Investig. 2011;121(10):4138–49.CrossRefPubMedPubMedCentral

46.

Westerterp M, Gourion-Arsiquaud S, Murphy AJ, et al. Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways. Cell Stem Cell. 2012;11(2):195–206.CrossRefPubMedPubMedCentral

47.

Yvan-Charvet L, Pagler T, Gautier EL, et al. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science. 2010;328(5986):1689–93.CrossRefPubMedPubMedCentral

48.

Wang Y, Viscarra J, Kim SJ, Sul HS. Transcriptional regulation of hepatic lipogenesis. Nat Rev Mol Cell Biol. 2015;16(11):678–89. https://doi.org/10.1038/nrm4074.CrossRefPubMedPubMedCentral

49.

Im SS, Yousef L, Blaschitz C, Liu JZ, Edwards RA, Young SG, et al. Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a. Cell Metab. 2011;13(5):540–9. https://doi.org/10.1016/j.cmet.2011.04.001.CrossRefPubMedPubMedCentral

50.

•• Oishi Y, Spann NJ, Link VM, et al. SREBP1 contributes to resolution of pro-inflammatory TLR4 signaling by reprogramming fatty acid metabolism. Cell Metab. 2017;25(2):412–27. This paper highlights the role of SREBP1c in macrophages during the resolution phase thus providing novel insights into lipid requirements according to different functional stage of immune cells. CrossRefPubMed

51.

Ito A, Hong C, Rong X, et al. LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling. elife. 2015;4:e08009.CrossRefPubMedPubMedCentral

52.

Brown MS, Goldstein JL. Lipoprotein receptors and genetic control of cholesterol metabolism in cultured human cells. Die Naturwissenschaften. 1975;62(8):385–9. https://doi.org/10.1007/BF00625346.CrossRefPubMed

53.

Bensinger SJ, Bradley MN, Joseph SB, Zelcer N, Janssen EM, Hausner MA, et al. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell. 2008;134(1):97–111. https://doi.org/10.1016/j.cell.2008.04.052.CrossRefPubMedPubMedCentral

54.

Kidani Y, Elsaesser H, Hock MB, et al. Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity. Nat Immunol. 2013;14(5):489–99.CrossRefPubMedPubMedCentral

55.

Buck MD, Sowell RT, Kaech SM, Pearce EL. Metabolic instruction of immunity. Cell. 2017;169(4):570–86. https://doi.org/10.1016/j.cell.2017.04.004.CrossRefPubMed

56.

Haas R, Smith J, Rocher-Ros V, et al. Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions. PLoS Biol. 2015;13(7):e1002202.CrossRefPubMedPubMedCentral

57.

• Mauro C, Smith J, Cucchi D, et al. Obesity-induced metabolic stress leads to biased effector memory CD4+ T cell differentiation via PI3K p110delta-Akt-mediated signals. Cell Metab. 2017;25(3):593–609. This paper provides evidence of a direct role of saturated free fatty acids in priming CD4 T cell differentiation and trafficking to inflammatory sites independently of the metabolic status of the host. CrossRefPubMedPubMedCentral

58.

Ni K, O’Neill HC. The role of dendritic cells in T cell activation. Immunol Cell Biol. 1997;75(3):223–30. https://doi.org/10.1038/icb.1997.35.CrossRefPubMed

59.

Steinman RM. Linking innate to adaptive immunity through dendritic cells. Novartis Found Symp. 2006;279:101–9. discussion 109–113, 216–109PubMed

60.

Zernecke A. Dendritic cells in atherosclerosis: evidence in mice and humans. Arterioscler Thromb Vasc Biol. 2015;35(4):763–70. https://doi.org/10.1161/ATVBAHA.114.303566.CrossRefPubMed

61.

•• Westerterp M, Gautier EL, Ganda A, et al. Cholesterol accumulation in dendritic cells links the inflammasome to acquired immunity. Cell Metab. 2017;25(6):1294–1304 e1296. This paper identifies an essential role of cholesterol efflux pathway mediated by ABCA1/G1 in maintaining immune tolerance. CrossRefPubMed

62.

Charles-Schoeman C. Cardiovascular disease and rheumatoid arthritis: an update. Curr Rheumatol Rep. 2012;14(5):455–62. https://doi.org/10.1007/s11926-012-0271-5.CrossRefPubMedPubMedCentral

63.

Ronda N, Favari E, Borghi MO, et al. Impaired serum cholesterol efflux capacity in rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis. 2014;73(3):609–15.CrossRefPubMed

64.

Wang SH, Yuan SG, Peng DQ, Zhao SP. HDL and ApoA-I inhibit antigen presentation-mediated T cell activation by disrupting lipid rafts in antigen presenting cells. Atherosclerosis. 2012;225(1):105–14. https://doi.org/10.1016/j.atherosclerosis.2012.07.029.CrossRefPubMed

65.

Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–81.CrossRefPubMed

66.

Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–78.CrossRefPubMed

67.

Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res. 2017;120(1):229–43.CrossRefPubMedPubMedCentral

68.

Boekholdt SM, Hovingh GK, Mora S, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64(5):485–94. https://doi.org/10.1016/j.jacc.2014.02.615.CrossRefPubMedPubMedCentral

69.

Kinlay S. Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis. J Am Coll Cardiol. 2007;49(20):2003–9. https://doi.org/10.1016/j.jacc.2007.01.083.CrossRefPubMed

70.

Catapano AL, Pirillo A, Norata GD. Vascular inflammation and low-density lipoproteins: is cholesterol the link? A lesson from the clinical trials. Br J Pharmacol. 2017;174(22):3973–85.CrossRefPubMed

71.

Noveck R, Stroes ES, Flaim JD, et al. Effects of an antisense oligonucleotide inhibitor of C-reactive protein synthesis on the endotoxin challenge response in healthy human male volunteers. J Am Heart Assoc. 2014;3(4):e001084. https://doi.org/10.1161/JAHA.114.001084.CrossRefPubMedPubMedCentral

72.

Lane T, Wassef N, Poole S, et al. Infusion of pharmaceutical-grade natural human C-reactive protein is not proinflammatory in healthy adult human volunteers. Circ Res. 2014;114(4):672–6.CrossRefPubMed

73.

Elliott P, Chambers JC, Zhang W, Clarke R, Hopewell JC, Peden JF, et al. Genetic loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA. 2009;302(1):37–48. https://doi.org/10.1001/jama.2009.954.CrossRefPubMedPubMedCentral

74.

Zacho J, Tybjaerg-Hansen A, Jensen JS, Grande P, Sillesen H, Nordestgaard BG. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med. 2008;359(18):1897–908. https://doi.org/10.1056/NEJMoa0707402.CrossRefPubMed

75.

Wensley F, Gao P, Burgess S, et al. Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data. BMJ. 2011;342:d548.CrossRefPubMed

76.

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–22. https://doi.org/10.1056/NEJMoa1615664.CrossRefPubMed

77.

Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA. 2016;316(22):2373–84.CrossRefPubMed

78.

•• Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119–31. This trial shows the cardiovascular benefit of inhibiting IL-1ß, thus supporting the inflammatory hypothesis of atherosclerosis. CrossRefPubMed

79.

Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P, Glynn RJ, et al. Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390(10105):1833–42. https://doi.org/10.1016/S0140-6736(17)32247-X.CrossRefPubMed

80.

Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol. 2015;15(2):104–16. https://doi.org/10.1038/nri3793.CrossRefPubMedPubMedCentral

81.

Rosenfeld ME. Inflammation and atherosclerosis: direct versus indirect mechanisms. Curr Opin Pharmacol. 2013;13(2):154–60. https://doi.org/10.1016/j.coph.2013.01.003.CrossRefPubMedPubMedCentral

82.

Elhage R, Jawien J, Rudling M, et al. Reduced atherosclerosis in interleukin-18 deficient apolipoprotein E-knockout mice. Cardiovasc Res. 2003;59(1):234–40.CrossRefPubMed

83.

Li JM, Eslami MH, Rohrer MJ, Dargon P, Joris I, Hendricks G, et al. Interleukin 18 binding protein (IL18-BP) inhibits neointimal hyperplasia after balloon injury in an atherosclerotic rabbit model. J Vasc Surg. 2008;47(5):1048–57. https://doi.org/10.1016/j.jvs.2007.12.005.CrossRefPubMed

84.

Hueso M, De Ramon L, Navarro E, et al. Silencing of CD40 in vivo reduces progression of experimental atherogenesis through an NF-kappaB/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis. Atherosclerosis. 2016;255:80–9.CrossRefPubMed

85.

Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature. 1998;394(6689):200–3.CrossRefPubMed

86.

Schonbeck U, Sukhova GK, Shimizu K, Mach F, Libby P. Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice. Proc Natl Acad Sci U S A. 2000;97(13):7458–63. https://doi.org/10.1073/pnas.97.13.7458.CrossRefPubMedPubMedCentral

87.

Bot I, Ortiz Zacarias NV, de Witte WE, et al. A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy. Sci Rep. 2017;7(1):52. https://doi.org/10.1038/s41598-017-00104-z.CrossRefPubMedPubMedCentral

88.

Olzinski AR, Turner GH, Bernard RE, Karr H, Cornejo CA, Aravindhan K, et al. Pharmacological inhibition of C-C chemokine receptor 2 decreases macrophage infiltration in the aortic root of the human C-C chemokine receptor 2/apolipoprotein E-/- mouse: magnetic resonance imaging assessment. Arterioscler Thromb Vasc Biol. 2010;30(2):253–9. https://doi.org/10.1161/ATVBAHA.109.198812.CrossRefPubMed

89.

White HD, Held C, Stewart R, et al. Darapladib for preventing ischemic events in stable coronary heart disease. N Engl J Med. 2014;370(18):1702–11.CrossRefPubMed

90.

Silva LC, Ortigosa LC, Benard G. Anti-TNF-alpha agents in the treatment of immune-mediated inflammatory diseases: mechanisms of action and pitfalls. Immunotherapy. 2010;2(6):817–33. https://doi.org/10.2217/imt.10.67.CrossRefPubMed

91.

Ridker PM, MacFadyen JG, Everett BM, et al: Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial. Lancet. 2017. https://doi.org/10.1016/S0140-6736(17)32814-3.

92.

Everett BM, Pradhan AD, Solomon DH, Paynter N, MacFadyen J, Zaharris E, et al. Rationale and design of the Cardiovascular Inflammation Reduction Trial: a test of the inflammatory hypothesis of atherothrombosis. Am Heart J. 2013;166(2):199–207 e115. https://doi.org/10.1016/j.ahj.2013.03.018.CrossRefPubMedPubMedCentral

Title: The Interplay of Lipids, Lipoproteins, and Immunity in Atherosclerosis
Authors: Angela Pirillo
Fabrizia Bonacina
Giuseppe Danilo Norata
Alberico Luigi Catapano
Publication date: 01-03-2018
Publisher: Springer US
Published in: Current Atherosclerosis Reports / Issue 3/2018
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI: https://doi.org/10.1007/s11883-018-0715-0

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