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Progress and challenges in translating the biology of atherosclerosis

Nature volume 473, pages 317–325 (2011)Cite this article

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Abstract

Atherosclerosis is a chronic disease of the arterial wall, and a leading cause of death and loss of productive life years worldwide. Research into the disease has led to many compelling hypotheses about the pathophysiology of atherosclerotic lesion formation and of complications such as myocardial infarction and stroke. Yet, despite these advances, we still lack definitive evidence to show that processes such as lipoprotein oxidation, inflammation and immunity have a crucial involvement in human atherosclerosis. Experimental atherosclerosis in animals furnishes an important research tool, but extrapolation to humans requires care. Understanding how to combine experimental and clinical science will provide further insight into atherosclerosis and could lead to new clinical applications.

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Figure 1: Stages in the development of atherosclerotic lesions.
Figure 2: The intersection of inflammation and lipid metabolism modulates atherosclerosis and provides potential targets for therapeutic manipulation.

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References

  1. Glass, C. K. & Witztum, J. L. Atherosclerosis: the road ahead. Cell 104, 503–516 (2001).

    Article  CAS  PubMed  Google Scholar 

  2. Lusis, A. J. Atherosclerosis. Nature 407, 233–241 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Libby, P. Vascular biology of atherosclerosis: overview and state of the art. Am. J. Cardiol. 91, 3–6 (2003).

    Article  Google Scholar 

  4. Tabas, I., Williams, K. J. & Boren, J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 116, 1832–1844 (2007).

    Article  CAS  PubMed  Google Scholar 

  5. Majesky, M. W. Developmental basis of vascular smooth muscle diversity. Arterioscler. Thromb. Vasc. Biol. 27, 1248–1258 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Gimbrone, M. A. Jr, Topper, J. N., Nagel, T., Anderson, K. R. & Garcia-Cardeña, G. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann. NY Acad. Sci. 902, 230–240 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. 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  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bouhlel, M. A. et al. PPARg activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab. 6, 137–143 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. Tabas, I. Macrophage death and defective inflammation resolution in atherosclerosis. Nature Rev. Immunol. 10, 36–46 (2010).

    Article  CAS  Google Scholar 

  11. Libby, P. Molecular and cellular mechanisms of the thrombotic complication of atherosclerosis. J. Lipid Res. 50, S352–s357 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Steinberg, D. The Cholesterol Wars: the Skeptics vs. the Preponderance of Evidence 1st edn (Elsevier, 2007).

    Google Scholar 

  13. Goldstein, J. L. & Brown, M. S. The LDL receptor. Arterioscler. Thromb. Vasc. Biol. 29, 431–438 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Brown, M. S. & Goldstein, J. L. Heart attacks: gone with the century? Science 272, 629 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Libby, P. The forgotten majority: unfinished business in cardiovascular risk reduction. J. Am. Coll. Cardiol. 46, 1225–1228 (2005).

    Article  PubMed  Google Scholar 

  16. Cannon, C. P. et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N. Engl. J. Med. 350, 1495–1504 (2004). This study demonstrates the residual risk for patients who have survived an acute coronary syndrome despite intensive statin treatment.

    Article  CAS  PubMed  Google Scholar 

  17. Nissen, S. E. et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. J. Am. Med. Assoc. 295, 1556–1565 (2006).

    Article  CAS  Google Scholar 

  18. Tall, A. R., Yvan-Charvet, L., Terasaka, N., Pagler, T. & Wang, N. HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab. 7, 365–375 (2008).

    Article  CAS  PubMed  Google Scholar 

  19. Rye, K. A., Bursill, C. A., Lambert, G., Tabet, F. & Barter, P. J. The metabolism and anti-atherogenic properties of HDL. J. Lipid Res. 50, S195–S200 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Vaisar, T. et al. Shotgun proteomics implicates protease inhibition and complement activation in the antiinflammatory properties of HDL. J. Clin. Invest. 117, 746–756 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Brewer, H. B. Jr. High-density lipoproteins: a new potential therapeutic target for the prevention of cardiovascular disease. Arterioscler. Thromb. Vasc. Biol. 24, 387–391 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. Chapman, M. J., Le Goff, W., Guerin, M. & Kontush, A. Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors. Eur. Heart J. 31, 149–164 (2010).

    Article  CAS  PubMed  Google Scholar 

  23. Jahangiri, A. et al. HDL remodeling during the acute phase response. Arterioscler. Thromb. Vasc. Biol. 29, 261–267 (2009).

    Article  CAS  PubMed  Google Scholar 

  24. Asztalos, B. F. et al. Differential effects of HDL subpopulations on cellular ABCA1- and SR-BI-mediated cholesterol efflux. J. Lipid Res. 46, 2246–2253 (2005).

    Article  CAS  PubMed  Google Scholar 

  25. Barter, P. J. et al. Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 357, 2109–2122 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. Barter, P. J. & Kastelein, J. J. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J. Am. Coll. Cardiol. 47, 492–499 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Cannon, C. P. et al. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N. Engl. J. Med. 363, 2406–2415 (2010).

    Article  CAS  PubMed  Google Scholar 

  28. Nissen, S. E. et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. J. Am. Med. Assoc. 290, 2292–2300 (2003).

    Article  CAS  Google Scholar 

  29. Tardif, J. C. et al. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. J. Am. Med. Assoc. 297, 1675–1682 (2007).

    Article  Google Scholar 

  30. Navab, M. et al. Human apolipoprotein AI mimetic peptides for the treatment of atherosclerosis. Curr. Opin. Investig. Drugs 4, 1100–1104 (2003).

    CAS  PubMed  Google Scholar 

  31. Staels, B. Fibrates in CVD: a step towards personalised medicine. Lancet 375, 1847–1848 (2010).

    Article  PubMed  Google Scholar 

  32. Frick, M. H. et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. N. Engl. J. Med. 317, 1237–1245 (1987).

    Article  CAS  PubMed  Google Scholar 

  33. Robins, S. J. et al. Relation of gemfibrozil treatment and lipid levels with major coronary events. VA-HIT: a randomized controlled trial. J. Am. Med. Assoc. 285, 1585–1591 (2001).

    Article  CAS  Google Scholar 

  34. Jones, P. H. & Davidson, M. H. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am. J. Cardiol. 95, 120–122 (2005).

    Article  CAS  PubMed  Google Scholar 

  35. Keech, A. et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366, 1849–1861 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. Ginsberg, H. N. et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N. Engl. J. Med. 362, 1563–1574 (2010).

    Article  PubMed  Google Scholar 

  37. Taggart, A. K. et al. (D)-β-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J. Biol. Chem. 280, 26649–26652 (2005). This paper identifies a target of nicotinic acid action that may provide mechanistic insight into its mode of action.

    Article  CAS  PubMed  Google Scholar 

  38. Brown, B. G. & Zhao, X. Q. Nicotinic acid, alone and in combinations, for reduction of cardiovascular risk. Am. J. Cardiol. 101, 58B–62B (2008).

    Article  CAS  PubMed  Google Scholar 

  39. Duffy, D. & Rader, D. J. Update on strategies to increase HDL quantity and function. Nature Rev. Cardiol. 6, 455–463 (2009).

    Article  Google Scholar 

  40. Sarwar, N. et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 115, 450–458 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Gerstein, H. C. et al. Effects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med. 358, 2545–2559 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. Duckworth, W. et al. Glucose control and vascular complications in veterans with type 2 diabetes. N. Engl. J. Med. 360, 129–139 (2009).

    Article  CAS  PubMed  Google Scholar 

  43. Jun, M. et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 375, 1875–1884 (2010).

    Article  CAS  PubMed  Google Scholar 

  44. Siscovick, D. S., Lemaitre, R. N. & Mozaffarian, D. The fish story: a diet–heart hypothesis with clinical implications: n-3 polyunsaturated fatty acids, myocardial vulnerability, and sudden death. Circulation 107, 2632–2634 (2003).

    Article  PubMed  Google Scholar 

  45. Kawakami, A. et al. Toll-like receptor 2 mediates apolipoprotein CIII-induced monocyte activation. Circ. Res. 103, 1402–1409 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mullick, A. E., Tobias, P. S. & Curtiss, L. K. Modulation of atherosclerosis in mice by Toll-like receptor 2. J. Clin. Invest. 115, 3149–3156 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Eriksson, P., Nilsson, L., Karpe, F. & Hamsten, A. Very-low-density lipoprotein response element in the promoter region of the human plasminogen activator inhibitor-1 gene implicated in the impaired fibrinolysis of hypertriglyceridemia. Arterioscler. Thromb. Vasc. Biol. 18, 20–26 (1998).

    Article  CAS  PubMed  Google Scholar 

  48. Berliner, J. A. & Watson, A. D. A role for oxidized phospholipids in atherosclerosis. N. Engl. J. Med. 353, 9–11 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Steinberg, D. The LDL modification hypothesis of atherogenesis: an update. J. Lipid. Res. 50, S376–S381 (2009). A balanced weighing of the oxidized-lipid hypothesis of atherosclerosis from a pioneer in the field.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Steinberg, D. & Witztum, J. L. Oxidized low-density lipoprotein and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 30, 2311–2316 (2010).

    Article  CAS  PubMed  Google Scholar 

  51. Lonn, E. et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. J. Am. Med. Assoc. 293, 1338–1347 (2005).

    Article  Google Scholar 

  52. Lonn, E. et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N. Engl. J. Med. 354, 1567–1577 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Steinberg, D. & Witztum, J. L. Is the oxidative modification hypothesis relevant to human atherosclerosis? Circulation 105, 2107–2111 (2002).

    Article  PubMed  Google Scholar 

  54. Tardif, J. C. et al. Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebo-controlled trial. Lancet 371, 1761–1768 (2008).

    Article  CAS  PubMed  Google Scholar 

  55. Serruys, P. W. et al. Effects of the direct lipoprotein-associated phospholipase A2 inhibitor darapladib on human coronary atherosclerotic plaque. Circulation 118, 1172–1182 (2008).

    Article  CAS  PubMed  Google Scholar 

  56. Jonasson, L., Holm, J., Skalli, O., Bondjers, G. & Hansson, G. K. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis 6, 131–138 (1986).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  58. Hartvigsen, K. et al. The role of innate immunity in atherogenesis. J. Lipid. Res. 50, S388–393 (2008).

  59. Andersson, J., Libby, P. & Hansson, G. K. Adaptive immunity and atherosclerosis. Clin. Immunol. 134, 33–46 (2010).

    Article  CAS  PubMed  Google Scholar 

  60. Palinski, W., Miller, E. & Witztum, J. L. Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis. Proc. Natl Acad. Sci. USA 92, 821–825 (1995).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  61. Maron, R. et al. Mucosal administration of heat shock protein-65 decreases atherosclerosis and inflammation in aortic arch of low-density lipoprotein receptor-deficient mice. Circulation 106, 1708–1715 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. Hansson, G. K. & Nilsson, J. Vaccination against atherosclerosis? Induction of atheroprotective immunity. Semin. Immunopathol. 31, 95–101 (2009).

    Article  CAS  PubMed  Google Scholar 

  63. Hermansson, A. et al. Inhibition of T cell response to native low-density lipoprotein reduces atherosclerosis. J. Exp. Med. 207, 1081–1093 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Robertson, A. K. et al. Disruption of TGF-β signaling in T cells accelerates atherosclerosis. J. Clin. Invest. 112, 1342–1350 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ait-Oufella, H. et al. Natural regulatory T cells control the development of atherosclerosis in mice. Nature Med. 12, 178–180 (2006).

    Article  CAS  PubMed  Google Scholar 

  66. van Es, T. et al. Attenuated atherosclerosis upon IL-17R signaling disruption in LDLr deficient mice. Biochem. Biophys. Res. Commun. 388, 261–265 (2009).

    Article  CAS  PubMed  Google Scholar 

  67. Taleb, S., Tedgui, A. & Mallat, Z. Interleukin-17: friend or foe in atherosclerosis? Curr. Opin. Lipidol. 21, 404–408 (2010).

    Article  CAS  PubMed  Google Scholar 

  68. Taleb, S. et al. Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. J. Exp. Med. 206, 2067–2077 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Madhur, M. S. et al. Role of interleukin 17 in inflammation, atherosclerosis, and vascular function in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. doi:10.1161/ATVBAHA.111.227629 2011 (7 April 2011).

  70. Cheng, X. et al. Inhibition of IL-17A in atherosclerosis. Atherosclerosis 215, 471–474 (2011).

    Article  CAS  PubMed  Google Scholar 

  71. Caligiuri, G., Nicoletti, A., Poirier, B. & Hansson, G. K. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J. Clin. Invest. 109, 745–753 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Ait-Oufella, H. et al. B cell depletion reduces the development of atherosclerosis in mice. J. Exp. Med. 207, 1579–1587 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Bentzon, J. F. & Falk, E. Atherosclerotic lesions in mouse and man: is it the same disease? Curr. Opin. Lipidol. 21, 434–440 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Nussenblatt, R. B. et al. National Institutes of Health Center for Human Immunology Conference, September 2009. Ann. NY Acad. Sci. 1200, E1–E23 (2010). A recent compilation of some of the distinctions between the human and mouse immune systems.

    Article  PubMed  Google Scholar 

  75. Tran, D. Q., Ramsey, H. & Shevach, E. M. Induction of FOXP3 expression in naive human CD4+FOXP3− T cells by T-cell receptor stimulation is transforming growth factor-β-dependent but does not confer a regulatory phenotype. Blood 110, 2983–2990 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Raes, G., Van den Bergh, R., De Baetselier, P. & Ghassabeh, G. H. Arginase-1 and Ym1 are markers for murine, but not human, alternatively activated myeloid cells. J. Immunol. 174, 6561–6562 (2005).

    Article  CAS  PubMed  Google Scholar 

  77. Hansson, G. K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 352, 1685–1695 (2005).

    Article  CAS  PubMed  Google Scholar 

  78. Libby, P. & Ridker, P. M. Inflammation and atherothrombosis. J. Am. Coll. Cardiol. 48, 33–46 (2006).

    Article  CAS  Google Scholar 

  79. Grosser, T., Fries, S. & FitzGerald, G. A. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J. Clin. Invest. 116, 4–15 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ridker, P. M. et al. C-reactive protein levels and outcomes after statin therapy. N. Engl. J. Med. 352, 20–28 (2005).

    Article  CAS  PubMed  Google Scholar 

  81. Ridker, P. M. et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 373, 1175–1182 (2009).

    Article  CAS  PubMed  Google Scholar 

  82. Harismendy, O. et al. 9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response. Nature 470, 264–268 (2011).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  83. Schunkert, H. et al. Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease. Circulation 117, 1675–1684 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Kathiresan, S. et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nature Genet. 40, 189–197 (2008).

    Article  CAS  PubMed  Google Scholar 

  85. Morgan, T. M., Krumholz, H. M., Lifton, R. P. & Spertus, J. A. Nonvalidation of reported genetic risk factors for acute coronary syndrome in a large-scale replication study. J. Am. Med. Assoc. 297, 1551–1561 (2007). This paper describes the lack of reproducibility of associations between single-nucleotide polymorphisms and atherosclerotic outcomes.

    Article  CAS  Google Scholar 

  86. Paynter, N. P. et al. Association between a literature-based genetic risk score and cardiovascular events in women. J. Am. Med. Assoc. 303, 631–637 (2010). This study shows that a panel of reproducible genetic variants from genome-wide association studies does not improve cardiovascular risk prediction.

    Article  CAS  Google Scholar 

  87. Ridker, P. M. et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N. Engl. J. Med. 359, 2195–2207 (2008).

    Article  CAS  PubMed  Google Scholar 

  88. Libby, P., Di Carli, M. F. & Weissleder, R. The vascular biology of atherosclerosis and imaging targets. J. Nucl. Med. 51 (suppl. 1), 33S–37S (2010).

    Article  PubMed  Google Scholar 

  89. Altmann, S. W. et al. Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption. Science 303, 1201–1204 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  90. Cohen, J. C., Boerwinkle, E., Mosley, T. H. Jr & Hobbs, H. H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354, 1264–1272 (2006). This study identifies a new target for LDL lowering and provides evidence that life-long low LDL levels confer considerable cardiovascular protection, reinforcing and extending the results of short-term drug-intervention trials.

    Article  CAS  PubMed  Google Scholar 

  91. Brown, M. S. & Goldstein, J. L. Lowering LDL — not only how low, but how long? Science 311, 1721–1723 (2006).

    Article  CAS  PubMed  Google Scholar 

  92. Wang, C. Y., Liu, P. Y. & Liao, J. K. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol. Med. 14, 37–44 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Parmar, K. M. et al. Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J. Clin. Invest. 116, 49–58 (2006).

    Article  CAS  PubMed  Google Scholar 

  94. Ridker, P. M. Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the cardiovascular inflammation reduction trial (CIRT). J. Thromb. Haemost. 7 (suppl. s1), 332–339 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. Duewell, P. et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357–1361 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  96. Rajamaki, K. et al. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLoS ONE 5, e11765 (2010).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

We thank S. Karwacki for editorial assistance.

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Authors and Affiliations

  1. Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, 02115, Massachusetts, USA

    Peter Libby & Paul M Ridker

  2. Division of Cardiovascular Medicine, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Paul M Ridker

  3. Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, SE-17176, Sweden

    Göran K. Hansson

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Correspondence to Peter Libby.

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Competing interests

P.M.R. is a co-inventor on patents held by Brigham and Women's Hospital relating to the use of inflammatory biomarkers in the diagnosis and treatment of cardiovascular disease, that have been licensed to Siemens and AstraZeneca. G.K.H. is a co-inventor on patents relating to immunotherapy against atherosclerotic cardiovascular disease.

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Libby, P., Ridker, P. & Hansson, G. Progress and challenges in translating the biology of atherosclerosis. Nature 473, 317–325 (2011). https://doi.org/10.1038/nature10146

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