Current Cardiovascular Risk Reports

, Volume 7, Issue 2, pp 102–107 | Cite as

Myeloperoxidase and Atherosclerosis



Myeloperoxidase (MPO), a member of the peroxidase family, emerged as a major player in the initiation and propagation of atherosclerotic cardiovascular disease (CVD). Evidence for its role in atherosclerosis include that MPO: a) induces endothelial dysfunction, b) modifies physiologically functional high density lipoprotein (HDL) into “dysfunctional HDL”, c) converts low density lipoprotein (LDL) into more atherogenic modified LDL form, and d) induces endothelial cell death and tissue factor expression involved in plaque vulnerability. Elevated levels of blood MPO are associated with CVD, predict incident risks for myocardial infarction and cardiac death in subjects with acute coronary syndrome, and predict future risk of coronary artery disease (CAD) in healthy individuals. In this article, we review current understandings on the role of MPO in pathophysiological processes involved in atherosclerosis and CVD.


Myeloperoxidase Atherosclerosis Cardiovascular disease Coronary artery disease High density lipoproteins Low density lipoproteins Niacin Statins Inflammation Apolipoprotein AI Neutrophils 



This work has been supported, in part, by Veterans Affairs Merit Review Programs and Southern California Institute for Research and Education.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Klebanoff SJ. Oxygen metabolism and the toxic properties of phagocytes. Ann Intern Med. 1980;93:480–9.PubMedGoogle Scholar
  2. 2.
    • Baetta R, Corsini A. Role of polymorphonuclear neutrophils in atherosclerosis: current state and future perspectives. Atherosclerosis. 2010;210:1–13. A comprehensive review on the role of neutrophils in atherosclerosis.PubMedCrossRefGoogle Scholar
  3. 3.
    Zheng R, Brennan ML, Fu X, et al. Association between myeloperoxidase and risk of coronary artery disease. JAMA. 2001;286:2136–42.CrossRefGoogle Scholar
  4. 4.
    Brennan ML, Penn MS, Van Lente F, et al. Prognostic value of myeloperoxidase in patients with chest pain. N Eng J Med. 2003;349:1595–604.CrossRefGoogle Scholar
  5. 5.
    Baldus S, Heeschen C, Meinertz T, et al. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003;108:1440–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Meuwese MC, Stroes ES, Hazen SL, et al. Serum myeloperoxidase levels are associated with future risk of coronary artery disease in apparently healthy individuals. J Am Coll Cardiol. 2007;50:159–65.PubMedCrossRefGoogle Scholar
  7. 7.
    • Tang WH, Katz R, Brennan ML, et al. Usefulness of myeloperoxidase levels in healthy elderly subjects to predict risk of developing heart failure. Am J Cardiol. 2009;103:1269–74. This is a case–control study showing serum MPO levels are associated with the risk of future development of coronary artery disease in healthy subjects.PubMedCrossRefGoogle Scholar
  8. 8.
    Wong ND, Gransar H, Narula J, et al. Myeloperoxidase, subclinical atherosclerosis, and cardiovascular disease events. J Am Coll Cardiol Img. 2009;2:1093–9.Google Scholar
  9. 9.
    Mocatta TJ, Pilbrow AP, Cameron VA, et al. Plasma levels of myeloperoxidase predict mortality after myocardial infarction. J Am Coll Cardiol. 2007;49:1993–2000.PubMedCrossRefGoogle Scholar
  10. 10.
    Karakas M, Koenig W, Zierer A, et al. Myeloperoxidase is associated with incident coronary heart disease independently of traditional risk factors: results from the MONICA/KORA Augsburg study. J Intern Med. 2012;271:43–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Ferrante G, Nakano M, Prati F, et al. High levels of systemic myeloperoxidase are associated with coronary plaque erosion in patients with acute coronary syndromes: a clinicopathological study. Circulation. 2010;122:2505–13.PubMedCrossRefGoogle Scholar
  12. 12.
    Tavora FR, Ripple M, Li L, et al. Monocyte and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques. BMC Cardiovasc Disord. 2009;9:27–33.PubMedCrossRefGoogle Scholar
  13. 13.
    Naruko T, Ueda M, Haze K, et al. Neutrophil infiltration of culprit lesions in acute coronary syndromes. Circulation. 2002;106:2894–900.PubMedCrossRefGoogle Scholar
  14. 14.
    Kutter D, Devaquet P, Vanderstocken G, et al. Consequences of total and subtotal myeloperoxidase deficiency: risk or benefit? Acta Haematol. 2000;104:10–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Nikpoor B, Turecki G, Fournier C, et al. A functional myeloperoxidase polymorphic variant is associated with coronary artery diseasein French-Canadians. Am Heart J. 2001;142:336–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Pecoits-Filho R, Stenvinkel P, Marchlewska A, et al. A functional variant of the myeloperoxidase gene is associated with cardiovascular disease in end-stage renal disease patients. Kidney Int. 2003;84:172–6.CrossRefGoogle Scholar
  17. 17.
    Asselbergs FW, Tervaert JW, Tio RA, et al. Prognostic value of myeloperoxidase in patients with chest pain. N Eng J Med. 2004;350:516–8.CrossRefGoogle Scholar
  18. 18.
    Stefanescu A, Braun S, Ndrepepa G, et al. Prognostic value of plasma myeloperoxidase concentration in patients with stable coronary artery disease. Am Heart J. 2008;155:356–60.PubMedCrossRefGoogle Scholar
  19. 19.
    Kubala L, Lu G, Baldus S, et al. Plasma levels of myeloperoxidase are not elevated in patients with stable coronary artery disease. Clin Chim Acta. 2008;394:59–62.PubMedCrossRefGoogle Scholar
  20. 20.
    Eggers KM, Dellborg M, Johnston N, et al. Myeloperoxidase is not useful for the early assessment of patients with chest pain. Clin Biochem. 2010;43:240–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Brugger-Anderson T, Aarstoy H, Grundt H, et al. The long-term prognostic value of multiple biomarkers following a myocardial infarction. Thromb Res. 2008;123:60–6.CrossRefGoogle Scholar
  22. 22.
    Weiss SJ. Tissue distruction by neutrophils. N Eng J Med. 1989;320:365–76.CrossRefGoogle Scholar
  23. 23.
    Chen Y, Hashiguchi N, Yip L, et al. Hypertonic saline enhances neutrophil elastase release through activation of P2 and A3 receptors. Am J Physiol. 2006;290:C1051–9.CrossRefGoogle Scholar
  24. 24.
    Junger WG, Hyot DB, Davis RE, et al. Hypertonicity regulates the function of human neutrophils by modulating chemoattractant receptor signaling and activating mitogen-activated protein kinase p38. J Clin Invest. 1998;101:2768–79.PubMedCrossRefGoogle Scholar
  25. 25.
    Mocsai A, Jakus Z, Vontus T, et al. Kinase pathways in chemoattractant-induced degranulation of neutrophils: role of p38 mitogen-activated protein kinase activated by Src family kinases. J Immunol. 2000;164:4321–31.PubMedGoogle Scholar
  26. 26.
    Yan SR, Berton G. Regulation of Src family tyrosine kinase activities in adherent human neutrophils. J Biol Chem. 1996;271:23464–71.PubMedCrossRefGoogle Scholar
  27. 27.
    Brumell JH, Burkhardt AL, Bolen JB, et al. Endogenous reactive oxygen intermediates activate tyrosine kinases in human neutrophils. J Biol Chem. 1996;271:1455–61.PubMedCrossRefGoogle Scholar
  28. 28.
    Daughetty A, Dunn JL, Rateri DL, et al. Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions. J Clin Invest. 1994;94:437–44.CrossRefGoogle Scholar
  29. 29.
    Hazen SL, Gaut JP, Crowley JR, et al. Elevated levels of protein-bound p-hydroxyphenylacetaldehyde, an amino acid derived aldehyde generated by myeloperoxidase, are present in human fatty streaks, intermediate lesions, and advanced atherosclerotic lesions. Biochem J. 2000;352:693–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Ross R. Atherosclerosis-an inflammatory disease. New Eng J Med. 1999;340:115–26.PubMedCrossRefGoogle Scholar
  31. 31.
    Landmesser U, Hornig B, Drexler H. Endothelial function. A critical determinant in atherosclerosis. Circulation. 2004;109(Suppl I):II-27–II-33.Google Scholar
  32. 32.
    Ignarro LJ, Napoli C. Novel features of nitric oxide, endothelial nitric oxide synthase, and atherosclerosis. Curr Diab Rep. 2005;5:17–23.PubMedCrossRefGoogle Scholar
  33. 33.
    Abu-Soud HM, Hazen SL. Nitric oxide is a physiological substrate for mammalian peroxidases. J Biol Chem. 2000;275:37524–32.PubMedCrossRefGoogle Scholar
  34. 34.
    Nicholls SJ, Hazen SL. Myeloperoxidase and Cardiovascular disease. Arterioscler Thromb Vasc Biol. 2005;25:1102–11.PubMedCrossRefGoogle Scholar
  35. 35.
    Eiserich JP, Baldus S, Brennan ML, et al. Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science. 2002;296:2391–4.PubMedCrossRefGoogle Scholar
  36. 36.
    Rudolph TK, Wipper S, Reiter B, et al. Myeloperoxidase deficiency preserves vasomotor function in humans. Eur Heart J. 2011;33:1625–34.PubMedCrossRefGoogle Scholar
  37. 37.
    Vita JA, Brennan ML, Gokce N, et al. Serum myeloperoxidase levels independently predict endothelial dysfunction in humans. Circulation. 2004;110:1134–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem. 1997;272:20963–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Goldstein JL, Ho YK, Basu SK, Brown MS. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoproteins, producing massive cholesterol deposition. Proc Natl Acad Sci USA. 1979;76:333–7.Google Scholar
  40. 40.
    Hazen SL, Heinecke JW. 3-chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima. J Clin Invest. 1997;99:2075–81.PubMedCrossRefGoogle Scholar
  41. 41.
    Podrez EA, Schmitt D, Hoff HF, et al. Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro. J Clin Invest. 1999;103:1547–60.PubMedCrossRefGoogle Scholar
  42. 42.
    Podrez EA, Febbraio M, Sheibani N, et al. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J Clin Invest. 2000;105:1095–108.PubMedCrossRefGoogle Scholar
  43. 43.
    Wang Z, Nicholls SJ, Rodriguez ER, et al. Protein carbamylation links inflammation, smoking, uremia, and atherogenesis. Nat Med. 2007;13:1176–84.PubMedCrossRefGoogle Scholar
  44. 44.
    Rader DJ. Mechanisms of disease: HDL metabolism as a target for novel therapies. Nat Clin Pract Cardiovasc Med. 2007;4:102–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Ansell BJ, Navab M, Hama S, et al. Inflammatory/anti-inflammatory properties of high density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation. 2003;108:2751–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Panzenboeck U, Raitmayer S, Reicher H, et al. Effects of reagent and enzymatically generated hypochlorite on physicochemical and metabolic properties of high density lipoproteins. J Biol Chem. 1997;272:29711–20.PubMedCrossRefGoogle Scholar
  47. 47.
    Bergt C, Pennathur S, Fu X, et al. The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABAA1-dependent cholesterol transport. Proc Natl Acad Sci USA. 2004;101:13032–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Pennathur S, Bergt C, Shao B, et al. Human atherosclerotic intima and blood of patients with established coronary artery disease contain high density lipoprotein damaged by reactive nitrogen species. J Biol Chem. 2004;27:42977–83.CrossRefGoogle Scholar
  49. 49.
    Zheng L, Nukuna B, Brennan ML, et al. Apolipoprotein is a selective target for myeloperoxidase catalyzed oxidation and functional impairment in subjects with cardiovascular disease. J Clin Invest. 2004;114:529–41.PubMedGoogle Scholar
  50. 50.
    Undurti A, Huang Y, Lupica JA, et al. Modification of HDL by myeloperoxidase generates a pro-inflammatory particle. J Biol Chem. 2009;284:30825–35.PubMedCrossRefGoogle Scholar
  51. 51.
    Shao B, Oda MN, Oram JF, et al. Myeloperoxidase: an inflammatory enzyme for generating dysfunctional high density lipoprotein. Curr Opin Cardiol. 2006;21:322–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Nicholls SJ, Hazen SL. Myeloperoxidase, modified lipoproteins, and atherogenesis. J Lipid Res. 2009;50:S346–51.PubMedCrossRefGoogle Scholar
  53. 53.
    Smith JD. Myeloperoxidase, inflammation, and dysfunctional HDL. J Clin Lipidol. 2010;4:382–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Sugiyama S, Kugiyama K, Aikawa M, et al. 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. 2004;24:1309–14.PubMedCrossRefGoogle Scholar
  55. 55.
    Hazen SL. Myeloperoxidase and plaque vulnerability. Arterioscler Thromb Vasc Biol. 2004;24:1143–6.PubMedCrossRefGoogle Scholar
  56. 56.
    Malle E, Furtmuller PG, Sattler W, et al. Myeloperoxidase: a target for drug development? Brit J Pharmacol. 2007;1–17.Google Scholar
  57. 57.
    Kumar AP, Reynolds WF. Statins downregulate myeloperoxidase gene expression in macrophages. Biochem Biophys Res Commun. 2005;331:442–51.PubMedCrossRefGoogle Scholar
  58. 58.
    Zhou T, Shou SH, Qi SS, et al. The effect of atorvastatin on serum myeloperoxidase and CRP levels in patients with acute coronary syndrome. Clin Chim Acta. 2006;368:168–72.PubMedCrossRefGoogle Scholar
  59. 59.
    Andreou I, Tousoulis D, Miliou A, et al. Effects of rosuvastatin on myeloperoxidase levels in patients with chronic heart failure. A randomized placebo-controlled study. Atherosclerosis. 2010;210:194–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Ganji SH, Xiong X, Kamanna VS, Kashyap ML. Niacin inhibits myeloperoxidase activity and oxidative degradation of HDL and apoAI in human leukocytic myeloid cell line HL-60: Impact on anti-infalmmatory properties of HDL. Atherosclerosis. 2009;10(2):e182.CrossRefGoogle Scholar
  61. 61.
    Ganji SH, Qin S, Zhang L, et al. Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells. Atherosclerosis. 2009;202:68–75.PubMedCrossRefGoogle Scholar
  62. 62.
    Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101:20B–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Wu BJ, Yan L, Charlton F, et al. Evidence that niacin inhibits acute vascular inflammation and improves endothelial dysfunction independent of changes in plasma lipids. Arterioscler Thromb Vasc Biol. 2010;30:968–75.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Atherosclerosis Research Center, Department of Veterans Affairs Healthcare System, Long Beach, California, and Department of MedicineUniversity of CaliforniaIrvineUSA
  2. 2.Atherosclerosis Research Center, Medical Research Service (09–151)Veterans Affairs Healthcare SystemLong BeachUSA

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