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:

Myeloid cell contributions to cardiovascular health and disease

Abstract

Recent advances in cell tracing and sequencing technologies have expanded our knowledge on leukocyte behavior. As a consequence, inflammatory cells, such as monocyte-derived macrophages, and their actions and products are increasingly being considered as potential drug targets for treatment of atherosclerosis, myocardial infarction and heart failure. Particularly promising developments are the identification of harmful arterial and cardiac macrophage subsets, the cells’ altered, sometimes even clonal production in hematopoietic organs, and epigenetically entrained memories of myeloid progenitors and macrophages in the setting of cardiovascular disease. Given the roles of monocytes and macrophages in host defense, intricately understanding the involved cellular subsets, sources and functions is essential for the design of precision therapeutics that preserve protective innate immunity. Here I review how new clinical and preclinical data, often linking the cardiovascular, immune and other organ systems, propel conceptual advances to a point where cardiovascular immunotherapy appears within reach.

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

Fig. 1: Hematopoiesis and CVD.
Fig. 2: The hematopoietic niche and CVD.
Fig. 3: Clonal hematopoiesis.

Similar content being viewed by others

References

  1. Ridker, P. M. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 377, 1119–1131 (2017).

    Article  PubMed  CAS  Google Scholar 

  2. Jaiswal, S. et al. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371, 2488–2498 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Jaiswal, S. et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N. Engl. J. Med. 377, 111–121 (2017).

    Article  PubMed  Google Scholar 

  4. Courties, G. et al. Ischemic stroke activates hematopoietic bone marrow stem cells. Circ. Res. 116, 407–417 (2015).

    Article  PubMed  CAS  Google Scholar 

  5. Dutta, P. et al. Myocardial infarction accelerates atherosclerosis. Nature 487, 325–329 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Heidt, T. et al. Chronic variable stress activates hematopoietic stem cells. Nat. Med. 20, 754–758 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Leuschner, F. et al. Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis. J. Exp. Med. 209, 123–137 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Murphy, A. J. et al. ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice. J. Clin. Invest. 121, 4138–4149 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Robbins, C. S. et al. Extramedullary hematopoiesis generates Ly-6Chigh monocytes that infiltrate atherosclerotic lesions. Circulation 125, 364–374 (2012).

    Article  PubMed  Google Scholar 

  10. 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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Yvan-Charvet, L. et al. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science 328, 1689–1693 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Ensan, S. et al. Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth. Nat. Immunol. 17, 159–168 (2016).

    Article  PubMed  CAS  Google Scholar 

  13. Epelman, S. et al. Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40, 91–104 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Hulsmans, M. et al. Macrophages facilitate electrical conduction in the heart. Cell 169, 510–522.e20 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. King, K. R. et al. IRF3 and type I interferons fuel a fatal response to myocardial infarction. Nat. Med. 23, 1481–1487 (2017).

    Article  PubMed  CAS  Google Scholar 

  16. Lavine, K. J. et al. Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart. Proc. Natl Acad. Sci. USA 111, 16029–16034 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Cochain, C. et al. Single-cell RNA-seq reveals the transcriptional landscape and heterogeneity of aortic macrophages in murine atherosclerosis. Circ. Res. https://doi.org/10.1161/CIRCRESAHA.117.312509 (2018).

  18. Winkels, H. et al. Atlas of the immune cell repertoire in mouse atherosclerosis defined by single-cell RNA-sequencing and mass cytometry. Circ. Res. https://doi.org/10.1161/CIRCRESAHA.117.312513 (2018).

  19. Epelman, S., Liu, P. P. & Mann, D. L. Role of innate and adaptive immune mechanisms in cardiac injury and repair. Nat. Rev. Immunol. 15, 117–129 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Heidt, T. et al. Differential contribution of monocytes to heart macrophages in steady-state and after myocardial infarction. Circ. Res. 115, 284–295 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Robbins, C. S. et al. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat. Med. 19, 1166–1172 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Nabel, E. G. & Braunwald, E. A tale of coronary artery disease and myocardial infarction. N. Engl. J. Med. 366, 54–63 (2012).

    Article  PubMed  CAS  Google Scholar 

  23. Ridker, P. M. Residual inflammatory risk: addressing the obverse side of the atherosclerosis prevention coin. Eur. Heart J. 37, 1720–1722 (2016).

    Article  PubMed  Google Scholar 

  24. Libby, P., Lichtman, A. H. & Hansson, G. K. Immune effector mechanisms implicated in atherosclerosis: from mice to humans. Immunity 38, 1092–1104 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Roufaiel, M. et al. CCL19–CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima. Nat. Immunol. 17, 1263–1272 (2016).

    Article  PubMed  CAS  Google Scholar 

  26. Pinto, A. R. et al. Age-related changes in tissue macrophages precede cardiac functional impairment. Aging (Albany NY) 6, 399–413 (2014).

    Article  Google Scholar 

  27. Pinto, A. R. et al. Revisiting cardiac cellular composition. Circ. Res. 118, 400–409 (2016).

    Article  PubMed  CAS  Google Scholar 

  28. Bajpai, G. et al. The human heart contains distinct macrophage subsets with divergent origins and functions. Nat. Med. in the press (2018).

  29. Leid, J. et al. Primitive embryonic macrophages are required for coronary development and maturation. Circ. Res. 118, 1498–1511 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Aurora, A. B. et al. Macrophages are required for neonatal heart regeneration. J. Clin. Invest. 124, 1382–1392 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Molawi, K. et al. Progressive replacement of embryo-derived cardiac macrophages with age. J. Exp. Med. 211, 2151–2158 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hulsmans, M. et al. Cardiac macrophages promote diastolic dysfunction. J. Exp. Med. 215, 423–440 (2018).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  33. Medzhitov, R. Toll-like receptors and innate immunity. Nat. Rev. Immunol. 1, 135–145 (2001).

    Article  PubMed  CAS  Google Scholar 

  34. Frustaci, A. et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 96, 1180–1184 (1997).

    Article  PubMed  CAS  Google Scholar 

  35. Yamashita, T. et al. Recruitment of immune cells across atrial endocardium in human atrial fibrillation. Circ. J. 74, 262–270 (2010).

    Article  PubMed  CAS  Google Scholar 

  36. Aviles, R. J. et al. Inflammation as a risk factor for atrial fibrillation. Circulation 108, 3006–3010 (2003).

    Article  PubMed  Google Scholar 

  37. Dernellis, J. & Panaretou, M. Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation. Eur. Heart J. 25, 1100–1107 (2004).

    Article  PubMed  CAS  Google Scholar 

  38. Shankman, L. S. et al. KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nat. Med. 21, 628–637 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. McArdle, S., Chodaczek, G., Ray, N. & Ley, K. Intravital live cell triggered imaging system reveals monocyte patrolling and macrophage migration in atherosclerotic arteries. J. Biomed. Opt. 20, 26005 (2015).

    Article  PubMed  CAS  Google Scholar 

  40. McArdle, S., Mikulski, Z. & Ley, K. Live cell imaging to understand monocyte, macrophage, and dendritic cell function in atherosclerosis. J. Exp. Med. 213, 1117–1131 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Wang, Y. et al. Mitochondrial fission promotes the continued clearance of apoptotic cells by macrophages. Cell 171, 331–345.e22 (2017).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  42. Nowotschin, S. & Hadjantonakis, A. K. Use of KikGR a photoconvertible green-to-red fluorescent protein for cell labeling and lineage analysis in ES cells and mouse embryos. BMC Dev. Biol. 9, 49 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Quintar, A. et al. Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis. Circ. Res. 120, 1789–1799 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Nahrendorf, M. et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J. Exp. Med. 204, 3037–3047 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Yan, X. et al. Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction. J. Mol. Cell. Cardiol. 62, 24–35 (2013).

    Article  PubMed  CAS  Google Scholar 

  46. Hilgendorf, I. et al. Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium. Circ. Res. 114, 1611–1622 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. van der Laan, A. M. et al. Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir. Eur. Heart J. 35, 376–385 (2014).

    Article  PubMed  CAS  Google Scholar 

  48. Li, W. et al. Heart-resident CCR2+ macrophages promote neutrophil extravasation through TLR9/MyD88/CXCL5 signaling. JCI Insight 1, e87315 (2016).

    PubMed  PubMed Central  Google Scholar 

  49. Carlin, L. M. et al. Nr4a1-dependent Ly6Clow monocytes monitor endothelial cells and orchestrate their disposal. Cell 153, 362–375 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Walter, W. et al. Deciphering the dynamic transcriptional and post-transcriptional networks of macrophages in the healthy heart and after myocardial injury. Cell Reports 23, 622–636 (2018).

    Article  PubMed  CAS  Google Scholar 

  51. Sager, H. B. et al. Proliferation and recruitment contribute to myocardial macrophage expansion in chronic heart failure. Circ. Res. 119, 853–864 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Thomas, G. D. et al. Human blood monocyte subsets: a new gating strategy defined using cell surface markers identified by mass cytometry. Arterioscler. Thromb. Vasc. Biol. 37, 1548–1558 (2017).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  53. Lee, W. W. et al. PET/MRI of inflammation in myocardial infarction. J. Am. Coll. Cardiol. 59, 153–163 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Frangogiannis, N. G. et al. Resident cardiac mast cells degranulate and release preformed TNF-α, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation 98, 699–710 (1998).

    Article  PubMed  CAS  Google Scholar 

  55. Hofmann, U. et al. Activation of CD4+ T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice. Circulation 125, 1652–1663 (2012).

    Article  PubMed  CAS  Google Scholar 

  56. Saxena, A. et al. Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function. Am. J. Physiol. Heart Circ. Physiol. 307, H1233–H1242 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Zouggari, Y. et al. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat. Med. 19, 1273–1280 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Sager, H. B. et al. RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction. Sci. Transl. Med. 8, 342ra80 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Anzai, A. et al. The infarcted myocardium solicits GM-CSF for the detrimental oversupply of inflammatory leukocytes. J. Exp. Med. 214, 3293–3310 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Madjid, M., Awan, I., Willerson, J. T. & Casscells, S. W. Leukocyte count and coronary heart disease: implications for risk assessment. J. Am. Coll. Cardiol. 44, 1945–1956 (2004).

    Article  PubMed  Google Scholar 

  61. Weber, C. & Noels, H. Atherosclerosis: current pathogenesis and therapeutic options. Nat. Med. 17, 1410–1422 (2011).

    Article  PubMed  CAS  Google Scholar 

  62. Patel, A. A. et al. The fate and lifespan of human monocyte subsets in steady state and systemic inflammation. J. Exp. Med. 214, 1913–1923 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Dutta, P. et al. Myocardial infarction activates CCR2+ hematopoietic stem and progenitor cells. Cell Stem Cell 16, 477–487 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Sager, H. B. et al. Targeting interleukin-1β reduces leukocyte production after acute myocardial infarction. Circulation 132, 1880–1890 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Emami, H. et al. Splenic metabolic activity predicts risk of future cardiovascular events: demonstration of a cardiosplenic axis in humans. JACC Cardiovasc. Imaging 8, 121–130 (2015).

    Article  PubMed  Google Scholar 

  67. Tawakol, A. et al. Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. Lancet 389, 834–845 (2017).

    Article  PubMed  Google Scholar 

  68. Schmidt, M. I. et al. Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study. Lancet 353, 1649–1652 (1999).

    Article  PubMed  CAS  Google Scholar 

  69. Ferraro, F. et al. Diabetes impairs hematopoietic stem cell mobilization by altering niche function. Sci. Transl. Med. 3, 104ra101 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Nagareddy, P. R. et al. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab. 17, 695–708 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Oikawa, A. et al. Diabetes mellitus induces bone marrow microangiopathy. Arterioscler. Thromb. Vasc. Biol. 30, 498–508 (2010).

    Article  PubMed  CAS  Google Scholar 

  72. Nagareddy, P. R. et al. Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity. Cell Metab. 19, 821–835 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Rosengren, A. et al. Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study. Lancet 364, 953–962 (2004).

    Article  PubMed  Google Scholar 

  74. Méndez-Ferrer, S., Lucas, D., Battista, M. & Frenette, P. S. Haematopoietic stem cell release is regulated by circadian oscillations. Nature 452, 442–447 (2008).

    Article  PubMed  CAS  Google Scholar 

  75. Jan, M., Ebert, B. L. & Jaiswal, S. Clonal hematopoiesis. Semin. Hematol. 54, 43–50 (2017).

    Article  PubMed  Google Scholar 

  76. Zink, F. et al. Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood 130, 742–752 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Fuster, J. J. et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 355, 842–847 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Sano, S. et al. Tet2-mediated clonal hematopoiesis accelerates heart failure through a mechanism involving the IL-1β/NLRP3 inflammasome. J. Am. Coll. Cardiol. 71, 875–886 (2018).

    Article  PubMed  CAS  Google Scholar 

  79. Álvarez-Errico, D., Vento-Tormo, R., Sieweke, M. & Ballestar, E. Epigenetic control of myeloid cell differentiation, identity and function. Nat. Rev. Immunol. 15, 7–17 (2015).

    Article  PubMed  CAS  Google Scholar 

  80. Amit, I., Winter, D. R. & Jung, S. The role of the local environment and epigenetics in shaping macrophage identity and their effect on tissue homeostasis. Nat. Immunol. 17, 18–25 (2016).

    Article  PubMed  CAS  Google Scholar 

  81. Saeed, S. et al. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science 345, 1251086 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Bekkering, S. et al. Innate immune cell activation and epigenetic remodeling in symptomatic and asymptomatic atherosclerosis in humans in vivo. Atherosclerosis 254, 228–236 (2016).

    Article  PubMed  CAS  Google Scholar 

  83. Christ, A. et al. Western diet triggers NLRP3-dependent innate immune reprogramming. Cell 172, 162–175.e14 (2018).

    Article  PubMed  CAS  Google Scholar 

  84. Mitroulis, I. et al. Modulation of myelopoiesis progenitors is an integral component of trained immunity. Cell 172, 147–161.e12 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Ridker, P. M. 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 391, 319–328 (2018).

    Article  PubMed  CAS  Google Scholar 

  86. Brindle, K. New approaches for imaging tumour responses to treatment. Nat. Rev. Cancer 8, 94–107 (2008).

    Article  PubMed  CAS  Google Scholar 

  87. Wan, E. et al. Enhanced efferocytosis of apoptotic cardiomyocytes through myeloid–epithelial–reproductive tyrosine kinase links acute inflammation resolution to cardiac repair after infarction. Circ. Res. 113, 1004–1012 (2013).

    Article  PubMed  CAS  Google Scholar 

  88. Howangyin, K. Y. et al. Myeloid–epithelial–reproductive receptor tyrosine kinase and milk fat globule epidermal growth factor 8 coordinately improve remodeling after myocardial infarction via local delivery of vascular endothelial growth factor. Circulation 133, 826–839 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. A-Gonzalez, N. et al. Phagocytosis imprints heterogeneity in tissue-resident macrophages. J. Exp. Med. 214, 1281–1296 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. DeBerge, M. et al. MerTK cleavage on resident cardiac macrophages compromises repair after myocardial ischemia reperfusion injury. Circ. Res. 121, 930–940 (2017).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  91. Ziegler, K. A. et al. Local sympathetic denervation attenuates myocardial inflammation and improves cardiac function after myocardial infarction in mice. Cardiovasc. Res. 1, 291–299 (2018).

    Article  Google Scholar 

  92. Kain, V. et al. Resolvin D1 activates the inflammation resolving response at splenic and ventricular site following myocardial infarction leading to improved ventricular function. J. Mol. Cell. Cardiol. 84, 24–35 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Kaikita, K. et al. Targeted deletion of CC chemokine receptor 2 attenuates left ventricular remodeling after experimental myocardial infarction. Am. J. Pathol. 165, 439–447 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Dewald, O. et al. CCL2/monocyte chemoattractant protein-1 regulates inflammatory responses critical to healing myocardial infarcts. Circ. Res. 96, 881–889 (2005).

    Article  PubMed  CAS  Google Scholar 

  95. Majmudar, M. D. et al. Monocyte-directed RNAi targeting CCR2 improves infarct healing in atherosclerosis-prone mice. Circulation 127, 2038–2046 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Shiraishi, M. et al. Alternatively activated macrophages determine repair of the infarcted adult murine heart. J. Clin. Invest. 126, 2151–2166 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  97. 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).

    Article  PubMed  Google Scholar 

  98. Haubner, B. J. et al. Functional recovery of a human neonatal heart after severe myocardial infarction. Circ. Res. 118, 216–221 (2016).

    Article  PubMed  CAS  Google Scholar 

  99. Godwin, J. W., Pinto, A. R. & Rosenthal, N. A. Macrophages are required for adult salamander limb regeneration. Proc. Natl Acad. Sci. USA 110, 9415–9420 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Chow, A. et al. Bone marrow CD169+. macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J. Exp. Med. 208, 261–271 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Ben-Mordechai, T. et al. Macrophage subpopulations are essential for infarct repair with and without stem cell therapy. J. Am. Coll. Cardiol. 62, 1890–1901 (2013).

    Article  PubMed  Google Scholar 

  102. Serhan, C. N. & Savill, J. Resolution of inflammation: the beginning programs the end. Nat. Immunol. 6, 1191–1197 (2005).

    Article  PubMed  CAS  Google Scholar 

  103. Tothova, Z. et al. Multiplex CRISPR/Cas9-based genome editing in human hematopoietic stem cells models clonal hematopoiesis and myeloid neoplasia. Cell Stem Cell 21, 547–555.e8 (2017).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  104. Dever, D. P. et al. CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells. Nature 539, 384–389 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Yin, H. et al. Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing. Nat. Biotechnol. 35, 1179–1187 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Luo, Y. L. et al. Macrophage-specific in vivo gene editing using cationic lipid-assisted polymeric nanoparticles. ACS Nano 12, 994–1005 (2018).

    Article  PubMed  CAS  Google Scholar 

  107. Vandoorne, K. & Nahrendorf, M. Multiparametric imaging of organ system interfaces. Circ Cardiovasc Imaging 10, e005613 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Acar, M. et al. Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal. Nature 526, 126–130 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Lee, S. et al. Real-time in vivo imaging of the beating mouse heart at microscopic resolution. Nat. Commun. 3, 1054 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Lo Celso, C. et al. Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature 457, 92–96 (2009).

    Article  PubMed  CAS  Google Scholar 

  111. Abkowitz, J. L., Catlin, S. N., McCallie, M. T. & Guttorp, P. Evidence that the number of hematopoietic stem cells per animal is conserved in mammals. Blood 100, 2665–2667 (2002).

    Article  PubMed  CAS  Google Scholar 

  112. Morrison, S. J. & Scadden, D. T. The bone marrow niche for haematopoietic stem cells. Nature 505, 327–334 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Mendelson, A. & Frenette, P. S. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat. Med. 20, 833–846 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded in part by federal funds from the National Institutes of Health NS084863, HL139598, HL128264, HL117829, HL096576 and HL131495; the European Union’s Horizon 2020 research and innovation program under grant agreement no. 667837; the Global Research Lab (GRL) program (NRF-2015K1A1A2028228) of the National Research Foundation by the Korean government and the MGH Research Scholar Program.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Matthias Nahrendorf.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nahrendorf, M. Myeloid cell contributions to cardiovascular health and disease. Nat Med 24, 711–720 (2018). https://doi.org/10.1038/s41591-018-0064-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41591-018-0064-0

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