Top

Published in:

01-06-2009 | Review

Myeloid cells in atherosclerosis: initiators and decision shapers

Authors: Oliver Soehnlein, Christian Weber

Published in: Seminars in Immunopathology | Issue 1/2009

Abstract

Chronic inflammation is the underlying pathophysiological mechanism of atherosclerosis. Prominent suspects being involved in atherosclerosis are lymphocytes, platelets, and endothelial cells. However, recent advances suggest a potent role for myeloid leukocytes, specifically monocyte subsets, polymorphonuclear leukocytes, and mast cells. These three cell types are not just rapidly recruited or already reside in the vascular wall but also initiate and perpetuate core mechanisms in plaque formation and destabilization. Dendritic cell subsets as well as endothelial and smooth muscle progenitor cells may further emerge as important regulators of atheroprogression. To stimulate further investigations about the contribution of these myeloid cells, we highlight the current mechanistic understanding by which these cells tune atherosclerosis.

Ross R (1999) Atherosclerosis–an inflammatory disease. N Engl J Med 340:115–126. doi:10.1056/NEJM199901143400207 PubMedCrossRef

Hansson GK, Libby P (2006) The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 6:508–519. doi:10.1038/nri1882 PubMedCrossRef

Libby P (2008) The molecular mechanisms of the thrombotic complications of atherosclerosis. J Intern Med 263:517–527. doi:10.1111/j.1365-2796.2008.01965.x PubMedCrossRef

Zhang Y, Cliff WJ, Schoefl GI et al (1993) Plasma protein insudation as an index of early coronary atherogenesis. Am J Pathol 143:496–506PubMed

Maron DJ, Fazio S, Linton MF (2000) Current perspectives on statins. Circulation 101:207–213PubMed

Weitz-Schmidt G (2002) Statins as anti-inflammatory agents. Trends Pharmacol Sci 23:482–486. doi:10.1016/S0165-6147(02) 02077-1 PubMedCrossRef

Ferroni P, Martini F, Cardarello CM et al (2003) Enhanced interleukin-1beta in hypercholesterolemia: effects of simvastatin and low-dose aspirin. Circulation 108:1673–1675. doi:10.1161/01.CIR.0000094732.02060.27 PubMedCrossRef

Schmeck B, Beermann W, N'Guessan PD et al (2008) Simvastatin reduces Chlamydophila pneumoniae-mediated histone modifications and gene expression in cultured human endothelial cells. Circ Res 102:888–895. doi:10.1161/CIRCRESAHA.107.161307 PubMedCrossRef

Chandrasekar B, Mummidi S, Mahimainathan L et al (2006) Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappaB- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin. J Biol Chem 281:15099–15109. doi:10.1074/jbc.M600200200 PubMedCrossRef

10.

Soehnlein O, Eskafi S, Schmeisser A et al (2004) Atorvastatin induces tissue transglutaminase in human endothelial cells. Biochem Biophys Res Commun 322:105–109. doi:10.1016/j.bbrc.2004.07.087 PubMedCrossRef

11.

Schönbeck U, Libby P (2004) Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents? Circulation 109:II18–II26. doi:10.1161/01.CIR.0000129505.34151.23 PubMedCrossRef

12.

Schmeisser A, Soehnlein O, Illmer T et al (2004) ACE inhibition lowers angiotensin II-induced chemokine expression by reduction of NF-kappaB activity and AT1 receptor expression. Biochem Biophys Res Commun 325:532–540. doi:10.1016/j.bbrc.2004.10.059 PubMedCrossRef

13.

Soehnlein O, Schmeisser A, Cicha I et al (2005) ACE inhibition lowers angiotensin-II-induced monocyte adhesion to HUVEC by reduction of p65 translocation and AT 1 expression. J Vasc Res 42:399–407. doi:10.1159/000087340 PubMedCrossRef

14.

Kuvin JT, Kimmelstiel CD (1999) Infectious causes of atherosclerosis. Am Heart J 137:216–226. doi:10.1053/hj.1999.v137.92261 PubMedCrossRef

15.

Epstein SE, Zhu J, Burnett MS et al (2000) Infection and atherosclerosis: potential roles of pathogen burden and molecular mimicry. Arterioscler Thromb Vasc Biol 20:1417–1420PubMed

16.

Heeneman S, Lutgens E, Schapira KB et al (2008) Control of atherosclerotic plaque vulnerability: insights from transgenic mice. Front Biosci 13:6289–6313. doi:10.2741/3155 PubMedCrossRef

17.

Weber C, Zernecke A, Libby P (2008) The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models. Nat Rev Immunol 8:802–815. doi:10.1038/nri2415 PubMedCrossRef

18.

George J (2008) Mechanisms of disease: the evolving role of regulatory T cells in atherosclerosis. Nat Clin Pract Cardiovasc Med 5:531–540. doi:10.1038/ncpcardio1279 PubMedCrossRef

19.

Watanabe T, Hirata M, Yoshikawa Y et al (1985) Role of macrophages in atherosclerosis. Sequential observations of cholesterol-induced rabbit aortic lesion by the immunoperoxidase technique using monoclonal antimacrophage antibody. Lab Invest 53:80–90PubMed

20.

Gown AM, Tsukada T, Ross R (1986) Human atherosclerosis. II. Immunocytochemical analysis of the cellular composition of human atherosclerotic lesions. Am J Pathol 125:191–207PubMed

21.

Ylitalo R, Oksala O, Ylä-Herttuala S et al (1994) Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. J Lab Clin Med 123:769–776PubMed

22.

Stoneman V, Braganza D, Figg N et al (2007) Monocyte/macrophage suppression in CD11b diphtheria toxin receptor transgenic mice differentially affects atherogenesis and established plaques. Circ Res 100:884–893. doi:10.1161/01.RES.0000260802.75766.00 PubMedCrossRef

23.

Napoli C, D'Armiento FP, Mancini FP et al (1997) Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest 100:2680–2690. doi:10.1172/JCI119813 PubMedCrossRef

24.

Ley K, Laudanna C, Cybulsky MI et al (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678–689. doi:10.1038/nri2156 PubMedCrossRef

25.

Zernecke A, Shagdarsuren E, Weber C (2008) Chemokines in atherosclerosis: an update. Arterioscler Thromb Vasc Biol 28:1897–1908. doi:10.1161/ATVBAHA.107.161174 PubMedCrossRef

26.

Weber C, Fraemohs L, Dejana E (2007) The role of junctional adhesion molecules in vascular inflammation. Nat Rev Immunol 7:467–477. doi:10.1038/nri2096 PubMedCrossRef

27.

Johnson-Tidey RR, McGregor JL, Taylor PR et al (1994) Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1. Am J Pathol 144:952–961PubMed

28.

Johnson RC, Chapman SM, Dong ZM et al (1997) Absence of P-selectin delays fatty streak formation in mice. J Clin Invest 99:1037–1043. doi:10.1172/JCI119231 PubMedCrossRef

29.

Katayama Y, Hidalgo A, Furie BC et al (2003) PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow: evidence for cooperation between E-selectin ligands and alpha4 integrin. Blood 102:2060–2067. doi:10.1182/blood-2003-04-1212 PubMedCrossRef

30.

Katayama Y, Hidalgo A, Chang J et al (2005) CD44 is a physiological E-selectin ligand on neutrophils. J Exp Med 201:1183–1189. doi:10.1084/jem.20042014 PubMedCrossRef

31.

Steegmaier M, Levinovitz A, Isenmann S et al (1995) The E-selectin-ligand ESL-1 is a variant of a receptor for fibroblast growth factor. Nature 373:615–620. doi:10.1038/373615a0 PubMedCrossRef

32.

Collins RG, Velji R, Guevara NV et al (2000) P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. J Exp Med 191:189–194. doi:10.1084/jem.191.1.189 PubMedCrossRef

33.

Dong ZM, Chapman SM, Brown AA, Frenette PS, Hynes RO, Wagner DD (1998) The combined role of P- and E-selectins in atherosclerosis. J Clin Invest 102:145–152. doi:10.1172/JCI3001 PubMedCrossRef

34.

Grage-Griebenow E, Flad HD, Ernst M (2001) Heterogeneity of human peripheral blood monocyte subsets. J Leukoc Biol 69:11–20PubMed

35.

Galkina E, Ley K (2007) Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol 27:2292–2301. doi:10.1161/ATVBAHA.107.149179 PubMedCrossRef

36.

Patel SS, Thiagarajan R, Willerson JT et al (1998) Inhibition of alpha4 integrin and ICAM-1 markedly attenuate macrophage homing to atherosclerotic plaques in ApoE-deficient mice. Circulation 97:75–81PubMed

37.

Nageh MF, Sandberg ET, Marotti KR et al (1997) Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice. Arterioscler Thromb Vasc Biol 17:1517–1520PubMed

38.

Cybulsky MI, Iiyama K, Li H et al (2001) A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 107:1255–1262. doi:10.1172/JCI11871 PubMedCrossRef

39.

Strauss-Ayali D, Conrad SM, Mosser DM (2007) Monocyte subpopulations and their differentiation patterns during infection. J Leukoc Biol 82:244–252. doi:10.1189/jlb.0307191 PubMedCrossRef

40.

Gordon S, Taylor PR (2006) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964. doi:10.1038/nri1733 CrossRef

41.

Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82. doi:10.1016/S1074-7613(03) 00174-2 PubMedCrossRef

42.

Weber C, Belge KU, von Hundelshausen P et al (2000) Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol 67:699–704PubMed

43.

Auffray C, Fogg D, Garfa M et al (2007) Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317:666–670. doi:10.1126/science.1142883 PubMedCrossRef

44.

Tacke F, Alvarez D, Kaplan TJ et al (2007) Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 117:185–194. doi:10.1172/JCI28549 PubMedCrossRef

45.

Braunersreuther V, Zernecke A, Arnaud C et al (2007) Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice. Arterioscler Thromb Vasc Biol 27:373–379. doi:10.1161/01.ATV.0000253886.44609.ae PubMedCrossRef

46.

Combadière C, Potteaux S, Rodero M et al (2008) Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation 117:1649–1657. doi:10.1161/CIRCULATIONAHA.107.745091 PubMedCrossRef

47.

Lesnik P, Haskell CA, Charo IF (2003) Decreased atherosclerosis in CX3CR1-/- mice reveals a role for fractalkine in atherogenesis. J Clin Invest 111:333–340PubMed

48.

Combadière C, Potteaux S, Gao JL et al (2003) Decreased atherosclerotic lesion formation in CX3CR1/apolipoprotein E double knockout mice. Circulation 107:1009–1016. doi:10.1161/01.CIR.0000057548.68243.42 PubMedCrossRef

49.

Huo Y, Ley K (2001) Adhesion molecules and atherogenesis. Acta Physiol Scand 173:35–43. doi:10.1046/j.1365-201X.2001.00882.x PubMedCrossRef

50.

An G, Wang H, Tang R et al (2008) P-selectin glycoprotein ligand-1 is highly expressed on Ly-6Chi monocytes and a major determinant for Ly-6Chi monocyte recruitment to sites of atherosclerosis in mice. Circulation 117:3227–3237. doi:10.1161/CIRCULATIONAHA.108.771048 PubMedCrossRef

51.

Swirski FK, Libby P, Aikawa E et al (2007) Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest 117:195–205. doi:10.1172/JCI29950 PubMedCrossRef

52.

Landsman L, Bar-On L, Zernecke A et al (2009) CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 113:963–972. doi:10.1182/blood-2008-07-170787 PubMedCrossRef

53.

Moore KJ, Freeman MW (2006) Scavenger receptors in atherosclerosis: beyond lipid uptake. Arterioscler Thromb Vasc Biol 26:1702–1711. doi:10.1161/01.ATV.0000229218.97976.43 PubMedCrossRef

54.

Babaev VR, Gleaves LA, Carter KJ et al (2000) Reduced atherosclerotic lesions in mice deficient for total or macrophage-specific expression of scavenger receptor-A. Arterioscler Thromb Vasc Biol 20:2593–2599PubMed

55.

Draude G, von Hundelshausen P, Frankenberger M et al (1999) Distinct scavenger receptor expression and function in the human CD14(+)/CD16(+) monocyte subset. Am J Physiol 276:H1144–H1149PubMed

56.

Nahrendorf M, Swirski FK, Aikawa E et al (2007) The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204:3037–3047. doi:10.1084/jem.20070885 PubMedCrossRef

57.

Trillo AA (1982) The cell population of aortic fatty streaks in African green monkeys with special reference to granulocytic cells. An ultrastructural study. Atherosclerosis 43:259–275. doi:10.1016/0021-9150(82) 90027-2 PubMedCrossRef

58.

Kawaguchi H, Mori T, Kawano T et al (1996) Band neutrophil count and the presence and severity of coronary atherosclerosis. Am Heart J 132:9–12. doi:10.1016/S0002-8703(96) 90384-1 PubMedCrossRef

59.

Sweetnam PM, Thomas HF, Yarnell JW et al (1997) Total and differential leukocyte counts as predictors of ischemic heart disease: the Caerphilly and Speedwell studies. Am J Epidemiol 145:416–421PubMed

60.

Naruko T, Ueda M, Haze K et al (2002) Neutrophil infiltration of culprit lesions in acute coronary syndromes. Circulation 106:2894–2900. doi:10.1161/01.CIR.0000042674.89762.20 PubMedCrossRef

61.

Zernecke A, Bot I, Djalali-Talab Y et al (2008) Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis. Circ Res 102:209–217. doi:10.1161/CIRCRESAHA.107.160697 PubMedCrossRef

62.

Eriksson EE, Xie X, Werr J et al (2001) Direct viewing of atherosclerosis in vivo: plaque invasion by leukocytes is initiated by the endothelial selectins. FASEB J 15:1149–1157. doi:10.1096/fj.00-0537com PubMedCrossRef

63.

Tabas I (2005) Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscler Thromb Vasc Biol 25:2255–2264. doi:10.1161/01.ATV.0000184783.04864.9f PubMedCrossRef

64.

Galligan C, Yoshimura T (2003) Phenotypic and functional changes of cytokine-activated neutrophils. Chem Immunol Allergy 83:24–44. doi:10.1159/000071555 PubMedCrossRef

65.

Rotzius P, Soehnlein O, Kenne E et al (2009) ApoE(−/−)/lysozyme M(EGFP/EGFP) mice as a versatile model to study monocyte and neutrophil trafficking in atherosclerosis. Atherosclerosis 202:111–118. doi:10.1016/j.atherosclerosis.2008.04.009 PubMedCrossRef

66.

Nathan C (2006) Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6:173–182. doi:10.1038/nri1785 PubMedCrossRef

67.

Oppenheim JJ, Yang D (2005) Alarmins: chemotactic activators of immune responses. Curr Opin Immunol 17:359–365. doi:10.1016/j.coi.2005.06.002 PubMedCrossRef

68.

Kai-Larsen Y, Agerberth B (2008) The role of the multifunctional peptide LL-37 in host defense. Front Biosci 13:3760–3767. doi:10.2741/2964 PubMedCrossRef

69.

Yang D, Biragyn A, Kwak LW et al (2002) Mammalian defensins in immunity: more than just microbicidal. Trends Immunol 23:291–296. doi:10.1016/S1471-4906(02) 02246-9 PubMedCrossRef

70.

Soehnlein O, Lindbom L (2008) Neutrophil-derived azurocidin alarms the immune system. J Leukoc Biol. doi:10.1189/jlb.0808495

71.

Chertov O, Yang D, Howard OM et al (2000) Leukocyte granule proteins mobilize innate host defenses and adaptive immune responses. Immunol Rev 177:68–78. doi:10.1034/j.1600-065X.2000.17702.x PubMedCrossRef

72.

Lee TD, Gonzalez ML, Kumar P et al (2002) CAP37, a novel inflammatory mediator: its expression in endothelial cells and localization to atherosclerotic lesions. Am J Pathol 160:841–848PubMed

73.

Soehnlein O, Xie X, Ulbrich H et al (2005) Neutrophil-derived heparin-binding protein (HBP/CAP37) deposited on endothelium enhances monocyte arrest under flow conditions. J Immunol 174:6399–6405PubMed

74.

von Hundelshausen P, Weber KS, Huo Y et al (2001) RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation 103:1772–1777

75.

Soehnlein O, Zernecke A, Eriksson EE et al (2008) Neutrophil secretion products pave the way for inflammatory monocytes. Blood 112:1461–1471. doi:10.1182/blood-2008-02-139634 PubMedCrossRef

76.

Gautam N, Olofsson AM, Herwald H et al (2001) Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked alteration of vascular permeability. Nat Med. 7:1123–1127PubMedCrossRef

77.

Soehnlein O, Oehmcke S, Ma X et al (2008) Neutrophil degranulation mediates severe lung damage triggered by streptococcal M1 protein. Eur Respir J 32:405–412. doi:10.1183/09031936.00173207 PubMedCrossRef

78.

Di Gennaro A, Kenne E, Wan M, et al (2009) Leukotrien B4-induced changes in vascular permeability are mediated by neutrophil release of heparin-binindg protein (HBP/CAP37/azurocidin). FASEB doi:0: fj.08-121277v1

79.

Soehnlein O, Kai-Larsen Y, Frithiof R et al (2008) Neutrophil primary granule proteins HBP and HNP1–3 boost bacterial phagocytosis by human and murine macrophages. J Clin Invest 118:3491–3502. doi:10.1172/JCI35740 PubMedCrossRef

80.

Påhlman LI, Mörgelin M, Eckert J et al (2006) Streptococcal M protein: a multipotent and powerful inducer of inflammation. J Immunol 177:1221–1228PubMed

81.

Cai TQ, Wright SD (1996) Human leukocyte elastase is an endogenous ligand for the integrin CR3 (CD11b/CD18, Mac-1, alpha M beta 2) and modulates polymorphonuclear leukocyte adhesion. J Exp Med 184:1213–1223. doi:10.1084/jem.184.4.1213 PubMedCrossRef

82.

Ribeiro-Gomes FL, Moniz-de-Souza MC, Alexandre-Moreira MS et al (2007) Neutrophils activate macrophages for intracellular killing of Leishmania major through recruitment of TLR4 by neutrophil elastase. J Immunol 179:3988–3994PubMed

83.

Li T, Wang H, He S (2006) Induction of interleukin-6 release from monocytes by serine proteinases and its potential mechanisms. Scand J Immunol 64:10–16. doi:10.1111/j.1365-3083.2006.01772.x PubMedCrossRef

84.

Michelsen KS, Wong MH, Shah PK et al (2004) Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc Natl Acad Sci USA 101:10679–10684. doi:10.1073/pnas.0403249101 PubMedCrossRef

85.

Luttun A, Lutgens E, Manderveld A et al (2004) Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growth. Circulation 109:1408–1414. doi:10.1161/01.CIR.0000121728.14930.DE PubMedCrossRef

86.

Eliason JL, Hannawa KK, Ailawadi G et al (2005) Neutrophil depletion inhibits experimental abdominal aortic aneurysm formation. Circulation 112:232–240. doi:10.1161/CIRCULATIONAHA.104.517391 PubMedCrossRef

87.

Pagano MB, Bartoli MA, Ennis TL et al (2007) Critical role of dipeptidyl peptidase I in neutrophil recruitment during the development of experimental abdominal aortic aneurysms. Proc Natl Acad Sci USA 104:2855–2860. doi:10.1073/pnas.0606091104 PubMedCrossRef

88.

Adkison AM, Raptis SZ, Kelley DG et al (2002) Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis. J Clin Invest 109:363–371PubMed

89.

Nicholls SJ, Hazen SL (2005) Myeloperoxidase and cardiovascular disease. Arterioscler Thromb Vasc Biol 25:1102–1111. doi:10.1161/01.ATV.0000163262.83456.6d PubMedCrossRef

90.

Sugiyama S, Kugiyama K, Aikawa M et al (2004) Hypochlorous acid, a macrophage product, induces endothelial apoptosis and tissue factor expression: involvement of myeloperoxidase-mediated oxidant in plaque erosion and thrombogenesis. Arterioscler Thromb Vasc Biol 24:1309–1314. doi:10.1161/01.ATV.0000131784.50633.4f PubMedCrossRef

91.

Brennan ML, Penn MS, Van Lente F et al (2003) Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 349:1595–1604. doi:10.1056/NEJMoa035003 PubMedCrossRef

92.

Steinberg D (2008) The LDL modification hypothesis of atherogenesis: an update. J Lipid Res (in press)

93.

Bdeir K, Cane W, Canziani G et al (1999) Defensin promotes the binding of lipoprotein(a) to vascular matrix. Blood 94:2007–2019PubMed

94.

Higazi AA, Lavi E, Bdeir K et al (1997) Defensin stimulates the binding of lipoprotein (a) to human vascular endothelial and smooth muscle cells. Blood 89:4290–4298PubMed

95.

Bobryshev YV (2006) Monocyte recruitment and foam cell formation in atherosclerosis. Micron 37:208–222. doi:10.1016/j.micron.2005.10.007 PubMedCrossRef

96.

Cheng J, Cui R, Chen CH et al (2007) Oxidized low-density lipoprotein stimulates p53-dependent activation of proapoptotic Bax leading to apoptosis of differentiated endothelial progenitor cells. Endocrinology 148:2085–2094. doi:10.1210/en.2006-1709 PubMedCrossRef

97.

Harrison D, Griendling KK, Landmesser U et al (2003) Role of oxidative stress in atherosclerosis. Am J Cardiol 91:7A–11A. doi:10.1016/S0002-9149(02) 03144-2 PubMedCrossRef

98.

Tanigawa T, Kitamura A, Yamagishi K et al (2003) Relationships of differential leukocyte and lymphocyte subpopulations with carotid atherosclerosis in elderly men. J Clin Immunol 23:469–476. doi:10.1023/B:JOCI.0000010423.65719.e5 PubMedCrossRef

99.

Rittersma SZ, Meuwissen M, van der Loos CM et al (2006) Eosinophilic infiltration in restenotic tissue following coronary stent implantation. Atherosclerosis 184:157–162. doi:10.1016/j.atherosclerosis.2005.03.049 PubMedCrossRef

100.

Thonnard-Neumann E, Fox RR, Taylor WL (1970) Basophilic leukocytes in the hyperlipemic rabbit. Blut 20:214–221. doi:10.1007/BF01632292 PubMedCrossRef

101.

Bischoff SC, Krieger M, Brunner T et al (1992) Monocyte chemotactic protein 1 is a potent activator of human basophils. J Exp Med 175:1271–1275. doi:10.1084/jem.175.5.1271 PubMedCrossRef

102.

Agis H, Willheim M, Sperr WR et al (1993) Monocytes do not make mast cells when cultured in the presence of SCF. Characterization of the circulating mast cell progenitor as a c-kit+, CD34+, Ly−, CD14−, CD17−, colony-forming cell. J Immunol 151:4221–4227PubMed

103.

Födinger M, Fritsch G, Winkler K et al (1994) Origin of human mast cells: development from transplanted hematopoietic stem cells after allogeneic bone marrow transplantation. Blood 84:2954–2959PubMed

104.

Kirshenbaum AS, Goff JP, Semere T et al (1999) Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13). Blood 94:2333–2342PubMed

105.

Galli SJ, Nakae S, Tsai M (2005) Mast cells in the development of adaptive immune responses. Nat Immunol 6:135–142. doi:10.1038/ni1158 PubMedCrossRef

106.

Kalesnikoff J, Galli SJ (2008) New developments in mast cell biology. Nat Immunol 9:1215–1223. doi:10.1038/ni.f.216 PubMedCrossRef

107.

Constantinides P (1953) Mast cells and susceptibility to experimental atherosclerosis. Science 117:505–506. doi:10.1126/science.117.3045.505 PubMedCrossRef

108.

Kovanen PT (2007) Mast cells and degradation of pericellular and extracellular matrices: potential contributions to erosion, rupture and intraplaque haemorrhage of atherosclerotic plaques. Biochem Soc Trans 35:857–861. doi:10.1042/BST0350857 PubMedCrossRef

109.

Bot I, de Jager SC, Zernecke A et al (2007) Perivascular mast cells promote atherogenesis and induce plaque destabilization in apolipoprotein E-deficient mice. Circulation 115:2516–2525. doi:10.1161/CIRCULATIONAHA.106.660472 PubMedCrossRef

110.

Sun J, Sukhova GK, Wolters PJ et al (2007) Mast cells promote atherosclerosis by releasing proinflammatory cytokines. Nat Med 13:719–724. doi:10.1038/nm1601 PubMedCrossRef

111.

Sun J, Sukhova GK, Yang M et al (2007) Mast cells modulate the pathogenesis of elastase-induced abdominal aortic aneurysms in mice. J Clin Invest 117:3359–3368. doi:10.1172/JCI31311 PubMedCrossRef

112.

Spanbroek R, Grabner R, Lotzer K et al (2003) Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proc Natl Acad Sci USA 100:1238–1243. doi:10.1073/pnas.242716099 PubMedCrossRef

113.

Qiu H, Gabrielsen A, Agardh HE et al (2006) Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Proc Natl Acad Sci USA 103:8161–8166. doi:10.1073/pnas.0602414103 PubMedCrossRef

114.

Dwyer JH, Allayee H, Dwyer KM et al (2004) Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. N Engl J Med 350:29–37. doi:10.1056/NEJMoa025079 PubMedCrossRef

115.

Helgadottir A, Manolescu A, Thorleifsson G et al (2004) The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet 36:233–239. doi:10.1038/ng1311 PubMedCrossRef

116.

Helgadottir A, Manolescu A, Helgason A et al (2006) A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Nat Genet 38:68–74. doi:10.1038/ng1692 PubMedCrossRef

117.

Mehrabian M, Allayee H, Wong J et al (2002) Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis susceptibility in mice. Circ Res 91:120–126. doi:10.1161/01.RES.0000028008.99774.7F PubMedCrossRef

118.

Zhao L, Moos MP, Gräbner R et al (2004) The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Nat Med 10:966–973. doi:10.1038/nm1099 PubMedCrossRef

119.

Ma H, Kovanen PT (1997) Degranulation of cutaneous mast cells induces transendothelial transport and local accumulation of plasma LDL in rat skin in vivo. J Lipid Res 38:1877–1887PubMed

120.

Lindstedt KA, Kokkonen JO, Kovanen PT (1992) Soluble heparin proteoglycans released from stimulated mast cells induce uptake of low density lipoproteins by macrophages via scavenger receptor-mediated phagocytosis. J Lipid Res 33:65–75PubMed

121.

Johnson JL, Jackson CL, Angelini GD et al (1998) Activation of matrix-degrading metalloproteinases by mast cell proteases in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 18:1707–1715PubMed

122.

Caughey GH (2007) Mast cell tryptases and chymases in inflammation and host defense. Immunol Rev 217:141–154. doi:10.1111/j.1600-065X.2007.00509.x PubMedCrossRef

123.

Miyazaki M, Takai S, Jin D et al (2006) Pathological roles of angiotensin II produced by mast cell chymase and the effects of chymase inhibition in animal models. Pharmacol Ther 112:668–676. doi:10.1016/j.pharmthera.2006.05.008 PubMedCrossRef

124.

Millonig G, Niederegger H, Rabl W et al (2001) Network of vascular-associated dendritic cells in intima of healthy young individuals. Arterioscler Thromb Vasc Biol 21:503–508PubMed

125.

Liu P, Yu YR, Spencer JA et al (2008) CX3CR1 deficiency impairs dendritic cell accumulation in arterial intima and reduces atherosclerotic burden. Arterioscler Thromb Vasc Biol 28:243–250. doi:10.1161/ATVBAHA.107.158675 PubMedCrossRef

126.

Bobryshev YV (2005) Dendritic cells in atherosclerosis: current status of the problem and clinical relevance. Eur Heart J 26:1700–1704. doi:10.1093/eurheartj/ehi282 PubMedCrossRef

127.

Yilmaz A, Lochno M, Traeg F et al (2004) Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques. Atherosclerosis 176:101–110. doi:10.1016/j.atherosclerosis.2004.04.027 PubMedCrossRef

128.

Yilmaz A, Reiss C, Tantawi O et al (2004) HMG-CoA reductase inhibitors suppress maturation of human dendritic cells: new implications for atherosclerosis. Atherosclerosis 172:85–93. doi:10.1016/j.atherosclerosis.2003.10.002 PubMedCrossRef

129.

Yilmaz A, Reiss C, Weng A et al (2006) Differential effects of statins on relevant functions of human monocyte-derived dendritic cells. J Leukoc Biol 79:529–538. doi:10.1189/jlb.0205064 PubMedCrossRef

130.

Shaposhnik Z, Wang X, Weinstein M et al (2007) Granulocyte macrophage colony-stimulating factor regulates dendritic cell content of atherosclerotic lesions. Arterioscler Thromb Vasc Biol 27:621–627. doi:10.1161/01.ATV.0000254673.55431.e6 PubMedCrossRef

131.

Zaguri R, Verbovetski I, Atallah M et al (2007) ‘Danger’ effect of low-density lipoprotein (LDL) and oxidized LDL on human immature dendritic cells. Clin Exp Immunol 149:543–552PubMed

132.

Katou F, Ohtani H, Nakayama T et al (2003) Differential expression of CCL19 by DC-Lamp + mature dendritic cells in human lymph node versus chronically inflamed skin. J Pathol 199:98–106. doi:10.1002/path.1255 PubMedCrossRef

133.

Lebre MC, Burwell T, Vieira PL et al (2005) Differential expression of inflammatory chemokines by Th1- and Th2-cell promoting dendritic cells: a role for different mature dendritic cell populations in attracting appropriate effector cells to peripheral sites of inflammation. Immunol Cell Biol 83:525–535. doi:10.1111/j.1440-1711.2005.01365.x PubMedCrossRef

134.

Tang HL, Cyster JG (1999) Chemokine up-regulation and activated T cell attraction by maturing dendritic cells. Science 284:819–822. doi:10.1126/science.284.5415.819 PubMedCrossRef

135.

Colonna M, Trinchieri G, Liu YJ (2004) Plasmacytoid dendritic cells in immunity. Nat Immunol 5:1219–1226. doi:10.1038/ni1141 PubMedCrossRef

136.

Niessner A, Sato K, Chaikof EL et al (2006) Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-alpha. Circulation 114:2482–2489. doi:10.1161/CIRCULATIONAHA.106.642801 PubMedCrossRef

137.

Asahara T, Murohara T, Sullivan A et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967. doi:10.1126/science.275.5302.964 PubMedCrossRef

138.

Hristov M, Weber C (2008) Endothelial progenitor cells in vascular repair and remodeling. Pharmacol Res 58:148–151. doi:10.1016/j.phrs.2008.07.008 PubMedCrossRef

139.

Hristov M, Weber C (2008) Ambivalence of progenitor cells in vascular repair and plaque stability. Curr Opin Lipidol 19:491–497. doi:10.1097/MOL.0b013e32830dfe33 PubMedCrossRef

140.

Schmeisser A, Garlichs CD, Zhang H et al (2001) Monocytes coexpress endothelial and macrophagocytic lineage markers and form cord-like structures in Matrigel under angiogenic conditions. Cardiovasc Res 49:671–680. doi:10.1016/S0008-6363(00) 00270-4 PubMedCrossRef

141.

Hristov M, Zernecke A, Liehn EA et al (2007) Regulation of endothelial progenitor cell homing after arterial injury. Thromb Haemost 98:274–277PubMed

142.

Schmidt-Lucke C, Rössig L, Fichtlscherer S et al (2005) Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 111:2981–2987. doi:10.1161/CIRCULATIONAHA.104.504340 PubMedCrossRef

143.

Hill JM, Zalos G, Halcox JP et al (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348:593–600. doi:10.1056/NEJMoa022287 PubMedCrossRef

144.

George J, Afek A, Abashidze A et al (2005) Transfer of endothelial progenitor and bone marrow cells influences atherosclerotic plaque size and composition in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 25:2636–2641. doi:10.1161/01.ATV.0000188554.49745.9e PubMedCrossRef

145.

Hristov M, Zernecke A, Bidzhekov K et al (2007) Importance of CXC chemokine receptor 2 in the homing of human peripheral blood endothelial progenitor cells to sites of arterial injury. Circ Res 100:590–597. doi:10.1161/01.RES.0000259043.42571.68 PubMedCrossRef

146.

Zernecke A, Schober A, Bot I et al (2005) SDF-1alpha/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res 96:784–791. doi:10.1161/01.RES.0000162100.52009.38 PubMedCrossRef

147.

Simper D, Stalboerger PG, Panetta CJ et al (2002) Smooth muscle progenitor cells in human blood. Circulation 106:1199–1204. doi:10.1161/01.CIR.0000031525.61826.A8 PubMedCrossRef

148.

Sugiyama S, Kugiyama K, Nakamura S et al (2006) Characterization of smooth muscle-like cells in circulating human peripheral blood. Atherosclerosis 187:351–362. doi:10.1016/j.atherosclerosis.2005.09.014 PubMedCrossRef

149.

Bentzon JF, Sondergaard CS, Kassem M et al (2007) Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice. Circulation 116:2053–2061. doi:10.1161/CIRCULATIONAHA.107.722355 PubMedCrossRef

150.

Zoll J, Fontaine V, Gourdy P et al (2008) Role of human smooth muscle cell progenitors in atherosclerotic plaque development and composition. Cardiovasc Res 77:471–480. doi:10.1093/cvr/cvm034 PubMedCrossRef

151.

Hillebrands JL, Klatter FA, van den Hurk BM et al (2001) Origin of neointimal endothelium and alpha-actin-positive smooth muscle cells in transplant arteriosclerosis. J Clin Invest 107:1411–1422. doi:10.1172/JCI10233 PubMedCrossRef

Title: Myeloid cells in atherosclerosis: initiators and decision shapers
Authors: Oliver Soehnlein
Christian Weber
Publication date: 01-06-2009
Publisher: Springer-Verlag
Published in: Seminars in Immunopathology / Issue 1/2009
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-009-0141-z

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2009

Advanced glycation end products and C-peptide—modulators in diabetic vasculopathy and atherogenesis

Atherosclerosis is an inflammatory disease

Obstructive sleep apnea, immuno-inflammation, and atherosclerosis

Innate and adaptive immunity in atherosclerosis

CRP and the risk of atherosclerotic events

The emerging role of the endocannabinoid system in cardiovascular disease

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage