Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Monocytes in atherosclerosis: subsets and functions

Abstract

Chronic inflammation drives atherosclerosis, the leading cause of cardiovascular disease. Over the past two decades, data have emerged showing that immune cells are involved in the pathogenesis of atherosclerotic plaques. The accumulation and continued recruitment of leukocytes are associated with the development of 'vulnerable' plaques. These plaques are prone to rupture, leading to thrombosis, myocardial infarction or stroke, all of which are frequent causes of death. Plaque macrophages account for the majority of leukocytes in plaques, and are believed to differentiate from monocytes recruited from circulating blood. However, monocytes represent a heterogenous circulating population of cells. Experiments are needed to address whether monocyte recruitment to plaques and effector functions, such as the formation of foam cells, the production of nitric oxide and reactive oxygen species, and proteolysis are critical for the development and rupture of plaques, and thus for the pathophysiology of atherosclerosis, as well as elucidate the precise mechanisms involved.

Key Points

  • Atherosclerosis has long been associated with chronic inflammation

  • The accumulation of macrophages correlates with atherosclerotic plaque progression and plaque rupture

  • Monocytes accumulate at sites of inflammation and have been reported to enter atherosclerotic plaques

  • Macrophages and foam cell are present in plaques and might derive from monocytes or from resident macrophages

  • Monocytes represent a heterogeneous population of cells with differences in phenotype, function and locomotion

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Inflammation and the role of blood monocytes.
Figure 2: Blood monocytes in atherosclerosis.
Figure 3: Heterogeneity of mouse monocyte subsets.
Figure 4: Monocyte recruitment.

Similar content being viewed by others

References

  1. Ross, R. Atherosclerosis—an inflammatory disease. N. Engl. J. Med. 340, 115–126 (1999).

    CAS  PubMed  Google Scholar 

  2. Gerrity, R. G., Naito, H. K., Richardson, M. & Schwartz, C. J. Dietary induced atherogenesis in swine. Morphology of the intima in prelesion stages. Am. J. Pathol. 95, 775–792 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Hansson, G. K. & Libby, P. The immune response in atherosclerosis: a double-edged sword. Nat. Rev. Immunol. 6, 508–519 (2006).

    CAS  PubMed  Google Scholar 

  4. Galkina, E. & Ley, K. Leukocyte influx in atherosclerosis. Curr. Drug Targets 8, 1239–1248 (2007).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  6. Heeneman, S., Lutgens, E., Schapira, K. B., Daemen, M. J. & Biessen, E. A. Control of atherosclerotic plaque vulnerability: insights from transgenic mice. Front. Biosci. 13, 6289–6313 (2008).

    CAS  PubMed  Google Scholar 

  7. Mallat, Z., Taleb, S., Ait-Oufella, H. & Tedgui, A. The role of adaptive T cell immunity in atherosclerosis. J. Lipid Res. 50 (Suppl.), S364–S369 (2009).

    PubMed  PubMed Central  Google Scholar 

  8. Auffray, C., Sieweke, M. H. & Geissmann, F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu. Rev. Immunol. 27, 669–692 (2009).

    CAS  PubMed  Google Scholar 

  9. Swirski, F. K. et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325, 612–616 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Geissmann, F., Jung, S. & Littman, D. R. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19, 71–82 (2003).

    CAS  PubMed  Google Scholar 

  11. Geissmann, F. et al. Blood monocytes: distinct subsets, how they relate to dendritic cells, and their possible roles in the regulation of T-cell responses. Immunol. Cell Biol. 86, 398–408 (2008).

    CAS  PubMed  Google Scholar 

  12. Tacke, F. & Randolph, G. J. Migratory fate and differentiation of blood monocyte subsets. Immunobiology 211, 609–618 (2006).

    CAS  PubMed  Google Scholar 

  13. Varol, C., Yona, S. & Jung, S. Origins and tissue-context-dependent fates of blood monocytes. Immunol. Cell Biol. 87, 30–38 (2009).

    PubMed  Google Scholar 

  14. Imhof, B. A. & Aurrand-Lions, M. Adhesion mechanisms regulating the migration of monocytes. Nat. Rev. Immunol. 4, 432–444 (2004).

    CAS  PubMed  Google Scholar 

  15. Ley, K., Laudanna, C., Cybulsky, M. I. & Nourshargh, S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat. Rev. Immunol. 7, 678–689 (2007).

    CAS  PubMed  Google Scholar 

  16. Greaves, D. R. & Gordon, S. The macrophage scavenger receptor at 30 years of age: current knowledge and future challenges. J. Lipid Res. 50 (Suppl.), S282–S286 (2009).

    PubMed  PubMed Central  Google Scholar 

  17. Galkina, E. & Ley, K. Immune and inflammatory mechanisms of atherosclerosis (*). Annu. Rev. Immunol. 27, 165–197 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Hahn, C. & Schwartz, M. A. Mechanotransduction in vascular physiology and atherogenesis. Nat. Rev. Mol. Cell Biol. 10, 53–62 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Bjornheden, T., Levin, M., Evaldsson, M. & Wiklund, O. Evidence of hypoxic areas within the arterial wall in vivo. Arterioscler. Thromb. Vasc. Biol. 19, 870–876 (1999).

    CAS  PubMed  Google Scholar 

  20. Virmani, R. et al. Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage. Arterioscler. Thromb. Vasc. Biol. 25, 2054–2061 (2005).

    CAS  PubMed  Google Scholar 

  21. Moulton, K. S. et al. Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc. Natl Acad. Sci. USA 100, 4736–4741 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Newby, A. C. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol. Rev. 85, 1–31 (2005).

    CAS  PubMed  Google Scholar 

  23. Fuster, V., Moreno, P. R., Fayad, Z. A., Corti, R. & Badimon, J. J. Atherothrombosis and high-risk plaque: part I: evolving concepts. J. Am. Coll. Cardiol. 46, 937–954 (2005).

    PubMed  Google Scholar 

  24. Primatesta, P. et al. Cardiovascular surveys: manual of operations. Eur. J. Cardiovasc. Prev. Rehabil. 14 (Suppl. 3), S43–S61 (2007).

    PubMed  Google Scholar 

  25. Shah, P. K. Molecular mechanisms of plaque instability. Curr. Opin. Lipidol. 18, 492–499 (2007).

    CAS  PubMed  Google Scholar 

  26. Llodra, J. et al. Emigration of monocyte-derived cells from atherosclerotic lesions characterizes regressive, but not progressive, plaques. Proc. Natl Acad. Sci. USA 101, 11779–11784 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Feig, J. E., Quick, J. S. & Fisher, E. A. The role of a murine transplantation model of atherosclerosis regression in drug discovery. Curr. Opin. Investig. Drugs 10, 232–238 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Randolph, G. J. Emigration of monocyte-derived cells to lymph nodes during resolution of inflammation and its failure in atherosclerosis. Curr. Opin. Lipidol. 19, 462–468 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Cybulsky, M. I., Won, D. & Haidari, M. Leukocyte recruitment to atherosclerotic lesions. Can. J. Cardiol. 20 (Suppl. B), 24B–28B (2004).

    PubMed  Google Scholar 

  30. Swirski, F. K., Weissleder, R. & Pittet, M. J. Heterogeneous in vivo behavior of monocyte subsets in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 29, 1424–1432 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Trogan, E. et al. Laser capture microdissection analysis of gene expression in macrophages from atherosclerotic lesions of apolipoprotein E-deficient mice. Proc. Natl Acad. Sci. USA 99, 2234–2239 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Palframan, R. T. et al. Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues. J. Exp. Med. 194, 1361–1373 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Qu, C. et al. Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes. J. Exp. Med. 200, 1231–1241 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Randolph, G. J., Beaulieu, S., Lebecque, S., Steinman, R. M. & Muller, W. A. Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science 282, 480–483 (1998).

    CAS  PubMed  Google Scholar 

  35. Taylor, P. R. & Gordon, S. Monocyte heterogeneity and innate immunity. Immunity 19, 2–4 (2003).

    CAS  PubMed  Google Scholar 

  36. Auffray, C. et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 3 17, 666–670 (2007).

    Google Scholar 

  37. Audoy-Remus, J. et al. Rod-shaped monocytes patrol the brain vasculature and give rise to perivascular macrophages under the influence of proinflammatory cytokines and angiopoietin-2. J. Neurosci. 28, 10187–10199 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Gordon, S. & Taylor, P. R. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5, 953–964 (2005).

    CAS  PubMed  Google Scholar 

  39. Napoli, C. et al. 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 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Ylitalo, R., Oksala, O., Yla-Herttuala, S. & Ylitalo, P. Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. J. Lab. Clin. Med. 123, 769–776 (1994).

    CAS  PubMed  Google Scholar 

  41. Stoneman, V. et al. Monocyte/macrophage suppression in CD11b diphtheria toxin receptor transgenic mice differentially affects atherogenesis and established plaques. Circ. Res. 100, 884–893 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Plump, A. S. & Breslow, J. L. Apolipoprotein E and the apolipoprotein E-deficient mouse. Annu. Rev. Nutr. 15, 495–518 (1995).

    CAS  PubMed  Google Scholar 

  43. Combadiere, C. et al. Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation 11 7, 1649–1657 (2008).

    Google Scholar 

  44. Zhang, S. H., Reddick, R. L., Piedrahita, J. A. & Maeda, N. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258, 468–471 (1992).

    CAS  PubMed  Google Scholar 

  45. Zernecke, A. et al. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis. Circ. Res. 102, 209–217 (2008).

    CAS  PubMed  Google Scholar 

  46. Swirski, F. K. et al. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J. Clin. Invest. 117, 195–205 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Tacke, F. et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J. Clin. Invest. 117, 185–194 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Dunon, D., Piali, L. & Imhof, B. A. To stick or not to stick: the new leukocyte homing paradigm. Curr. Opin. Cell Biol. 8, 714–723 (1996).

    CAS  PubMed  Google Scholar 

  49. Springer, T. A. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu. Rev. Physiol. 57, 827–872 (1995).

    CAS  PubMed  Google Scholar 

  50. Zernecke, A., Shagdarsuren, E. & Weber, C. Chemokines in atherosclerosis: an update. Arterioscler. Thromb. Vasc. Biol. 28, 1897–1908 (2008).

    CAS  PubMed  Google Scholar 

  51. Charo, I. F. & Taubman, M. B. Chemokines in the pathogenesis of vascular disease. Circ. Res. 95, 858–866 (2004).

    CAS  PubMed  Google Scholar 

  52. Saederup, N., Chan, L., Lira, S. A. & Charo, I. F. Fractalkine deficiency markedly reduces macrophage accumulation and atherosclerotic lesion formation in CCR2−/− mice: evidence for independent chemokine functions in atherogenesis. Circulation 117, 1642–1648 (2008).

    CAS  PubMed  Google Scholar 

  53. Lesnik, P., Haskell, C. A. & Charo, I. F. Decreased atherosclerosis in CX3CR1−/− mice reveals a role for fractalkine in atherogenesis. J. Clin. Invest. 111, 333–340 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Ancuta, P. et al. Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. J. Exp. Med. 197, 1701–1707 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Landsman, L. et al. CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 11 3, 963–972 (2009).

    Google Scholar 

  56. Serbina, N. V. & Pamer, E. G., Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat. Immunol. 7, 311–317 (2006).

    CAS  PubMed  Google Scholar 

  57. Woollard, K. J. & Chin-Dusting, J. Therapeutic targeting of p-selectin in atherosclerosis. Inflamm. Allergy Drug Targets. 6, 69–74 (2007).

    CAS  PubMed  Google Scholar 

  58. Girard, J. P. & Springer, T. A. High endothelial venules (HEVs): specialized endothelium for lymphocyte migration. Immunol. Today 16, 449–457 (1995).

    CAS  PubMed  Google Scholar 

  59. Johnson-Tidey, R. R., McGregor, J. L., Taylor, P. R. & Poston, R. N. Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1. Am. J. Pathol. 144, 952–961 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Johnson, R. C. et al. Absence of P-selectin delays fatty streak formation in mice. J. Clin. Invest. 99, 1037–1043 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Katayama, Y. et al. PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow: evidence for cooperation between E-selectin ligands and alpha4 integrin. Blood 1 02, 2060–2067 (2003).

    Google Scholar 

  62. Collins, R. G. et al. P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. J. Exp. Med. 191, 189–194 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Dong, Z. M. et al. The combined role of P- and E-selectins in atherosclerosis. J. Clin. Invest. 102, 145–152 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Woollard, K. J. Soluble bio-markers in vascular disease: much more than gauges of disease? Clin. Exp. Pharmacol. Physiol. 32, 233–240 (2005).

    CAS  PubMed  Google Scholar 

  65. Woollard, K. J. et al. Pathophysiological levels of soluble P-selectin mediate adhesion of leukocytes to the endothelium through Mac-1 activation. Circ. Res. 103, 1128–1138 (2008).

    CAS  PubMed  Google Scholar 

  66. Woollard, K. J. et al. Raised plasma soluble P-selectin in peripheral arterial occlusive disease enhances leukocyte adhesion. Circ. Res. 98, 149–156 (2006).

    CAS  PubMed  Google Scholar 

  67. Kisucka, J. et al. Elevated levels of soluble P-selectin in mice alter blood–brain barrier function, exacerbate stroke, and promote atherosclerosis. Blood 1 13, 6015–6022 (2009).

    Google Scholar 

  68. An, G. et al. 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 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  70. Galkina, E. & Ley, K. Vascular adhesion molecules in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 27, 2292–2301 (2007).

    CAS  PubMed  Google Scholar 

  71. Patel, S. S., Thiagarajan, R., Willerson, J. T. & Yeh, E. T. Inhibition of alpha4 integrin and ICAM-1 markedly attenuate macrophage homing to atherosclerotic plaques in ApoE-deficient mice. Circulation 97, 75–81 (1998).

    CAS  PubMed  Google Scholar 

  72. Nageh, M. F. et al. Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice. Arterioscler. Thromb. Vasc. Biol. 17, 1517–1520 (1997).

    CAS  PubMed  Google Scholar 

  73. Cybulsky, M. I. et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J. Clin. Invest. 107, 1255–1262 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Chatzizisis, Y. S. et al. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J. Am. Coll. Cardiol. 49, 2379–2393 (2007).

    CAS  PubMed  Google Scholar 

  75. Eriksson, E. E., Werr, J., Guo, Y., Thoren, P. & Lindbom, L. Direct observations in vivo on the role of endothelial selectins and alpha(4) integrin in cytokine-induced leukocyte–endothelium interactions in the mouse aorta. Circ. Res. 86, 526–533 (2000).

    CAS  PubMed  Google Scholar 

  76. Alvarez, A. et al. Direct evidence of leukocyte adhesion in arterioles by angiotensin II. Blood 104, 402–408 (2004).

    CAS  PubMed  Google Scholar 

  77. Caputo, K. E., Lee, D., King, M. R. & Hammer, D. A. Adhesive dynamics simulations of the shear threshold effect for leukocytes. Biophys. J. 92, 787–797 (2007).

    CAS  PubMed  Google Scholar 

  78. Chauhan, A. K. et al. ADAMTS13: a new link between thrombosis and inflammation. J. Exp. Med. 205, 2065–2074 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Bernardo, A. et al. Platelets adhered to endothelial cell-bound ultra-large von Willebrand factor strings support leukocyte tethering and rolling under high shear stress. J. Thromb. Haemost. 3, 562–570 (2005).

    CAS  PubMed  Google Scholar 

  80. Soehnlein, O., Lindbom, L. & Weber, C. Mechanisms underlying neutrophil-mediated monocyte recruitment. Blood 114, 4613–4623 (2009).

    CAS  PubMed  Google Scholar 

  81. Newby, A. C. Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability. Arterioscler. Thromb. Vasc. Biol. 28, 2108–2114 (2008).

    CAS  PubMed  Google Scholar 

  82. Hazen, S. L. Oxidized phospholipids as endogenous pattern recognition ligands in innate immunity. J. Biol. Chem. 283, 15527–15531 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Febbraio, M. et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J. Clin. Invest. 105, 1049–1056 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Kuchibhotla, S. et al. Absence of CD36 protects against atherosclerosis in ApoE knock-out mice with no additional protection provided by absence of scavenger receptor A I/II. Cardiovasc. Res. 78, 185–196 (2008).

    CAS  PubMed  Google Scholar 

  85. Moore, K. J. et al. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. J. Clin. Invest. 115, 2192–2201 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Park, Y. M., Febbraio, M. & Silverstein, R. L. CD36 modulates migration of mouse and human macrophages in response to oxidized LDL and may contribute to macrophage trapping in the arterial intima. J. Clin. Invest. 119, 136–145 (2009).

    CAS  PubMed  Google Scholar 

  87. Moreno, P. R., Purushothaman, K. R., Sirol, M., Levy, A. P. & Fuster, V. Neovascularization in human atherosclerosis. Circulation 113, 2245–2252 (2006).

    PubMed  Google Scholar 

  88. Barger, A. C., Beeuwkes, R., 3rd, Lainey, L. L. & Silverman, K. J. Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. N. Engl. J. Med. 310, 175–177 (1984).

    CAS  PubMed  Google Scholar 

  89. Celletti, F. L. et al. Vascular endothelial growth factor enhances atherosclerotic plaque progression. Nat. Med. 7, 425–429 (2001).

    CAS  PubMed  Google Scholar 

  90. Swirski, F. K. et al. Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease. Proc. Natl Acad. Sci. USA 103, 10340–10345 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Tabas, I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscler. Thromb. Vasc. Biol. 25, 2255–2264 (2005).

    CAS  PubMed  Google Scholar 

  92. Passlick, B., Flieger, D. & Ziegler-Heitbrock, H. W. Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood 74, 2527–2534 (1989).

    CAS  PubMed  Google Scholar 

  93. Strauss-Ayali, D., Conrad, S. M. & Mosser, D. M. Monocyte subpopulations and their differentiation patterns during infection. J. Leukoc. Biol. 82, 244–252 (2007).

    CAS  PubMed  Google Scholar 

  94. Weber, C. et al. Differential chemokine receptor expression and function in human monocyte subpopulations. J. Leukoc. Biol. 67, 699–704 (2000).

    CAS  PubMed  Google Scholar 

  95. Salomon, R. N., Underwood, R., Doyle, M. V., Wang, A. & Libby, P. Increased apolipoprotein E and c-fms gene expression without elevated interleukin 1 or 6 mRNA levels indicates selective activation of macrophage functions in advanced human atheroma. Proc. Natl Acad. Sci. USA 89, 2814–2818 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Schlitt, A. et al. CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels. Thromb. Haemost. 92, 419–424 (2004).

    CAS  PubMed  Google Scholar 

  97. Rothe, G. et al. Peripheral blood mononuclear phagocyte subpopulations as cellular markers in hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol. 16, 1437–1447 (1996).

    CAS  PubMed  Google Scholar 

  98. Tsujioka, H. et al. Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. J. Am. Coll. Cardiol. 54, 130–138 (2009).

    PubMed  Google Scholar 

  99. Wildgruber, M. et al. Monocyte subset dynamics in human atherosclerosis can be profiled with magnetic nano-sensors. PLoS One 4, e5663 (2009).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

K. J. Woollard is funded by a British Heart Foundation fellowship. Work in F. Geissmann's lab is supported by the Arthritis Research Campaign and the Medical Research Council (G0900867 Strategic Award).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kevin J. Woollard.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Woollard, K., Geissmann, F. Monocytes in atherosclerosis: subsets and functions. Nat Rev Cardiol 7, 77–86 (2010). https://doi.org/10.1038/nrcardio.2009.228

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrcardio.2009.228

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing