Myeloperoxidase (MPO) is a member of the heme peroxidase-cyclooxygenase superfamily. It is abundantly expressed in neutrophils and monocytes. During inflammation MPO is released from leukocytes and catalyzes the formation of several reactive species and tissue damage. In this article we present state of the art knowledge on the general properties, biosynthesis and processing and trafficking of MPO. The basic functions of MPO in inflammation and oxidative stress are discussed in detail. This article also summarizes the studies that investigated the relationship between MPO and cardiovascular disease. An overview of the assays for determination of MPO, the sample type and preanalytical procedures is given. Future studies are needed before this marker is introduced into routine clinical practice.
Agner K. Verdoperoxidase. A ferment isolated from leucocytes. Acta Physiol Scand 1941; 2 (Suppl. 8): 1-62.
Bos A, Wever R, Roos D. Characterization and quantification of the peroxidase in human monocytes. Biochim Biophys Acta 1978; 525: 37-44.
Daugherty A, Dunn JL, Rateri DL, Heinecke JW. Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions. J Clin Invest 1994; 94: 437-44.
Hansson M, Olsson I, Nauseef WM. Biosynthesis, processing, and sorting of human myeloperoxidase. Arch Biochem Biophys 2006; 445: 214-24.
Chevrier I, Tregouet DA, Massonnet-Castel S, Beaune P, Loriot MA. Myeloperoxidase genetic polymorphisms modulate human neutrophil enzyme activity: genetic determinants for atherosclerosis? Atherosclerosis 2006; 188: 150-4.
Hoy A, Tregouet D, Leininger-Muller B, Poirier O, Maurice M, Sass C, et al. Serum myeloperoxidase concentration in a healthy population: biological variations, familial resemblance and new genetic polymorphisms. Eur J Hum Genet 2001; 9: 780-6.
Nikpoor B, Turecki G, Fournier C, Theroux P, Rouleau GA. A functional myeloperoxidase polymorphic variant is associated with coronary artery disease in French-Canadians. Am Heart J 2001; 142: 336-9.
Makela R, Laaksonen R, Janatuinen T, Vesalainen R, Nuutila P, Jaakola O, et al. Myeloperoxidase gene variation and coronary flow reserve in young healthy men. J Biomed Sci 2004; 11: 59-64.
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 Suppl 2003; S172-6.
Asselbergs FW, Reynolds WF, Cohen-Tervaert JW, Jessurun GA, Tio RA. Myeloperoxidase polymorphism related to cardiovascular events in coronary artery disease. Am J Med 2004; 116: 429-30.
Wainstein RV, Wainstein MV, Ribeiro JP, et al. Association between myeloperoxidase polymorphisms and its plasma levels with severity of coronary artery disease. Clin Biochem 2010; 43: 57-62.
Domigan NM, Charlton TS, Duncan MW, Winterbourn CC, Kettle AJ. Chlorination of tyrosyl residues in peptides by myeloperoxidase and human neutrophils. J Biol Chem 1995; 270: 16542-8.
Hazen SL, Hsu FF, Mueller DM, Crowley JR, Heinecke JW. Human neutrophils employ chlorine gas as an oxidant during phagocytosis. J Clin Invest 1996; 98: 1283-9.
Eiserich JP, Hristova M, Cross CE, Jones AD, Freeman BA, Halliwell B, Van der Vliet A. Formation of nitric oxidederived inflammatory oxidants by myeloperoxidase in neutrophils. Nature 1998; 391: 393-7.
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.
Leeuwenburgh C, Rasmussen JE, Hsu FF, Mueller DM, Pennathur S, Heinecke JW. Mass spectrometric quantification of markers for protein oxidation by tyrosyl radical, copper, and hydroxyl radical in low density lipoprotein isolated from human atherosclerotic plaques. J Biol Chem 1997; 272: 3520-6.
Podrez EA, Febbraio M, Sheibani N, Schmitt D, Silverstein RL, Hajjar DP, Cohen PA, Frazier WA, Hoff HF, Hazen SL. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J Clin Invest 2000; 105: 1095-108.
Shao B, Oda MN, Oram JF, Heinecke JW. Myeloperoxidase: an oxidative pathway for generating dysfunctional high-density lipoprotein. Chem Res Toxicol 2010; 23: 447-54.
Wever RMF, Luscher TF, Cosentino F, Rabelink TJ. Atherosclerosis and the two faces of endothelial nitric oxide synthase. Circulation 1998; 97: 108-12.
Eiserich JP, Baldus S, Brennan ML, Ma W, Zhang C, Tousson A, et al. Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science 2002; 296: 2391-4.
Fu X, Kassim SY, Parks WC, Heinecke JW. Hypochlorous acid oxygenates the cysteine switch domain of promatrilysin (MMP-7). A mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase. J Biol Chem 2001; 276: 41279-87.
Sugiyama S, Okada Y, Sukhova GK, Virmani R, Heinecke JW, Libby P. Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. Am J Pathol 2001; 158: 879-91.
Baldus S, Eiserich JP, Mani A, Castro L, Figueroa M, Chumley P, et al. Endothelial transcytosis of myeloperoxidase confers specificity to vascular ECM proteins as targets of tyrosine nitration. J Clin Invest 2001; 108: 1759-70.
Sugiyama S, Kugiyama K, Aikawa M, Nakamura S, Ogawa H, Libby P. 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.
Meuwese MC, Stroes ES, Hazen SL, Van Miert JN, Kuivenhoven JA, Schaub RG, et al. Serum myeloperoxidase levels are associated with the future risk of coronary artery disease in apparently healthy individuals: the EPIC-Norfolk Prospective Population Study. J Am Coll Cardiol 2007; 50: 159-65.
Wong ND, Gransar H, Narula J, Shaw L, Moon JH, Miranda-Peats R, et al. Myeloperoxidase, subclinical atherosclerosis, and cardiovascular disease events. JACC Cardiovasc Imaging 2009; 2: 1093-9.
Brennan ML, Penn MS, Van Lente F, Nambi V, Shishehbor MH, Aviles RJ, et al. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 2003; 349: 1595-604.
Rudolph V, Goldmann BU, Bos C, Rudolph TK, Klinke A, Friedrichs K, et al. Diagnostic value of MPO plasma levels in patients admitted for suspected myocardial infarction. Int J Cardiol 2010 Sep 14.
Apple FS, Pearce LA, Chung A, Ler R, Murakami MM. Multiple biomarker use for detection of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome. Clin Chem 2007; 53: 874-81.
Apple FS, Smith SW, Pearce LA, Murakami MM. Assessment of the multiple-biomarker approach for diagnosis of myocardial infarction in patients presenting with symptoms suggestive of acute coronary syndrome. Clin Chem 2009; 55: 93-100.
Cheng ML, Chen CM, Gu PW, Ho HY, Chiu DT. Elevated levels of myeloperoxidase, white blood cell count and 3-chlorotyrosine in Taiwanese patients with acute myocardial infarction. Clin Biochem 2008; 41: 554-60.
Esporcatte R, Rey HC, Rangel FO, Rocha RM, Mendonça Filho HT, Dohmann HF, Albanesi Filho FM. Predictive value of myeloperoxidase to identify high risk patients admitted to the hospital with acute chest pain. Arq Bras Cardiol 2007; 89: 377-84.
Zhang R, Brennan ML, Fu X, Aviles RJ, Pearce GL, Penn MS, et al. Association between myeloperoxidase levels and risk of coronary artery disease. JAMA 2001; 286: 2136-42.
Baldus S, Heeschen C, Meinertz T, Zeiher AM, Eiserich JP, Munzel T, et al. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation 2003; 108: 1440-5.
Exner M, Minar E, Mlekusch W, Sabeti S, Amighi J, Lalouschek W, et al. Myeloperoxidase predicts progression of carotid stenosis in states of low high-density lipoprotein cholesterol. J Am Coll Cardiol 2006; 47: 2212-18.
Cavusoglu E, Ruwende C, Eng C, Chopra V, Yanamadala S, Clark LT, et al. Usefulness of baseline plasma myeloperoxidase levels as an independent predictor of myocardial infarction at two years in patients presenting with acute coronary syndrome. Am J Cardiol 2007; 99: 1364-8.
Mocatta TJ, Pilbrow AP, Cameron VA, Senthilmohan R, Frampton CM, Richards AM, Winterbourn CC. Plasma concentrations of myeloperoxidase predict mortality after myocardial infarction. J Am Coll Cardiol 2007; 49: 1993-2000.
Khan SQ, Kelly D, Quinn P, Davies JE, Ng LL. Myeloperoxidase aids prognostication together with N-terminal pro-B-type natriuretic peptide in high-risk patients with acute ST elevation myocardial infarction. Heart 2007; 93: 826-31.
Morrow DA, Sabatine MS, Brennan ML, De Lemos JA, Murphy SA, Ruff CT, et al. Concurrent evaluation of novel cardiac biomarkers in acute coronary syndrome: myeloperoxidase and soluble CD40 ligand and the risk of recurrent ischaemic events in TACTICS-TIMI 18. Eur Heart J 2008; 29: 1096-102.
Dominguez-Rodriguez A, Samimi-Fard S, Abreu-Gonzalez P, Garcia-Gonzalez MJ, Kaski JC. Prognostic value of admission myeloperoxidase levels in patients with ST-segment elevation myocardial infarction and cardiogenic shock. Am J Cardiol 2008; 101: 1537-40.
Karadag B, Vatan B, Hacioglu Y, Duman D, Baskurt M, Keles I, et al. Serum myeloperoxidase level predicts reperfusion in patients with myocardial infarction receiving thrombolytic therapy. Heart Vessels 2009; 24: 247-53.
Borges FK, Borges FK, Stella FS, et al. Serial analysis of C-reactive protein and myeloperoxidase in acute coronary syndrome. Clin Cardiol 2009; 32: E58-62.
Chang LT, Chua S, Sheu JJ, Wu CJ, Yeh KH, Yang CH, Yip HK. Level and prognostic value of serum myeloperoxidase in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Circ J 2009; 73: 726-31.
Yunoki K, Naruko T, Komatsu R, Shirai N, Nakagawa M, Sugioka K, et al. Relation of elevated levels of plasma myeloperoxidase to impaired myocardial microcirculation after reperfusion in patients with acute myocardial infarction. Am J Cardiol 2010; 105: 922-9.
Roman RM, Camargo PV, Borges FK, Rossini AP, Polanczyk CA. Prognostic value of myeloperoxidase in coronary artery disease: comparison of unstable and stable angina patients. Coron Artery Dis 2010; 21: 129-36.
Duzguncinar O, Yavuz B, Hazirolan T, Deniz A, Tokgozoglu SL, Akata D, Demirpence E. Plasma myeloperoxidase is related to the severity of coronary artery disease. Acta Cardiol 2008; 63: 147-52.
Ndrepepa G, Braun S, Mehilli J, Von Beckerath N, Schomig A, Kastrati A. Myeloperoxidase level in patients with stable coronary artery disease and acute coronary syndromes. Eur J Clin Invest 2008; 38: 90-6.
Tang WH, Wu Y, Nicholls SJ, Hazen SL. Plasma myeloperoxidase predicts incident cardiovascular risks in stable patients undergoing medical management for coronary artery disease. Clin Chem 2011; 57: 33-9.
Stefanescu A, Braun S, Ndrepepa G, Koppara T, Pavaci H, Mehilli J, et al. Prognostic value of plasma myeloperoxidase concentration in patients with stable coronary artery disease. Am Heart J 2008; 155: 356-60.
El Bejjani D, Hazen SL, Mackay W, Glass NE, Hulgan T, Tungsiripat M, McComsey GA. Higher plasma myeloperoxidase levels are not associated with an increased risk for cardiovascular events in HIV-infected adults. HIV Clin Trials 2008; 9: 207-11.
Kubala L, Lu G, Baldus S, Berglund L, Eiserich JP. Plasma levels of myeloperoxidase are not elevated in patients with stable coronary artery disease. Clin Chim Acta 2008; 394: 59-62.
Dominguez-Rodriguez A, Abreu-Gonzalez P, Kaski JC. Diurnal variation of circulating myeloperoxidase levels in patients with ST-segment elevation myocardial infarction. Int J Cardiol 2010; 144: 407-9.
Zelzer S, Khoschsorur G, Stettin M, Weihrauch G, Truschnig-Wilders M. Determination of myeloperoxidase in EDTA plasma: comparison of an enzyme-linked immunosorbent assay with a chemiluminescent automated immunoassay. Clin Chim Acta 2009; 406: 62-5.