Imaging Myeloperoxidase Activity in Cardiovascular Disease

Current Cardiovascular Imaging Reports

Volumn 4, Issue 1, 2011, Pages 24-31

  Ronald, John A ^a,b,c  

^a STANFORD UNIVERSITY   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c STANFORD UNIVERSITY   (United States)

Author keywords

Atherosclerosis; Bioluminescence imaging; Fluorescence imaging; Hydrogen peroxide; Hypochlorous acid; Magnetic resonance imaging; Molecular imaging; Monocyte macrophage; Myeloperoxidase; Myocardial infarction; Neutrophil; Oxidative stress; Single photon emission computed tomography; Stroke; Vulnerable plaque

Indexed keywords

EID: 84873076712     PISSN: 19419066     EISSN: 19419074     Source Type: Journal    
DOI: 10.1007/s12410-010-9056-2     Document Type: Review

References (51)

1. Hackam DG, Anand SS: Emerging risk factors for atherosclerotic vascular disease: a critical review of the evidence. JAMA 2003, 290(7): 932-940.
2. Lusis AJ: Atherosclerosis. Nature 2000, 407(6801): 233-241.
3. Libby P, Aikawa M: Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med 2002, 8(11): 1257-1262.
4. Casscells W, Naghavi M, Willerson JT: Vulnerable atherosclerotic plaque: a multifocal disease. Circulation 2003, 107(16): 2072-2075.
5. Falk E: Why do plaques rupture? Circulation 1992, 86(6 Suppl): III30-42.
6. Naghavi M, Libby P, Falk E, et al.: From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II. Circulation 2003, 108(15): 1772-1778.
7. Naghavi M, Libby P, Falk E, et al.: From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 2003, 108(14): 1664-1672.
8. Fuster V, Moreno PR, Fayad ZA, et al.: Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol 2005, 46(6): 937-954.
9. Geng Y-J, Libby P: Progression of atheroma: a struggle between death and procreation. Arteriosclerosis, Thrombosis, and Vascular Biology 2002, 22(9): 1370-1380.
10. Moreno PR, Purushothaman KR, Fuster V, et al.: Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation 2004, 110(14): 2032-2038.
11. Galis ZS, Sukhova GK, Lark MW, Libby P: Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994, 94(6): 2493-2503.
12. Nicholls SJ, Hazen SL: Myeloperoxidase and cardiovascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology 2005, 25(6): 1102-1111.
13. Klebanoff SJ: Myeloperoxidase: friend and foe. J Leukoc Biol 2005, 77(5): 598-625.
14. Schultz J, Kaminker K: Myeloperoxidase of the leucocyte of normal human blood. I. Content and localization. Arch Biochem Biophys 1962, 96: 465-467.
15. Bos A, Wever R, Roos D: Characterization and quantification of the peroxidase in human monocytes. Biochim Biophys Acta 1978, 525(1): 37-44.
16. 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(1): 437-444.
17. Sugiyama S, Okada Y, Sukhova GK, et al.: Macrophage myeloperoxidase regulation by granulocyte macrophage colony-stimulating factor in human atherosclerosis and implications in acute coronary syndromes. Am J Pathol 2001, 158(3): 879-891.
18. Hazen SL, Zhang R, Shen Z, et al.: Formation of nitric oxide-derived oxidants by myeloperoxidase in monocytes: pathways for monocyte-mediated protein nitration and lipid peroxidation In vivo. Circ Res 1999, 85(10): 950-958.
19. Nicholls SJ, Zheng L, Hazen SL: Formation of dysfunctional high-density lipoprotein by myeloperoxidase. Trends Cardiovasc Med 2005, 15(6): 212-219.
20. Nicholls SJ, Hazen SL: Myeloperoxidase, modified lipoproteins, and atherogenesis. J Lipid Res 2009, 50 Suppl: S346-351.
21. • Tavora FR, Ripple M, Li L, Burke AP: Monocytes and neutrophils expressing myeloperoxidase occur in fibrous caps and thrombi in unstable coronary plaques. BMC Cardiovasc Disord 2009, 9: 27. This article clearly shows that MPO is expressed in plaques with histological characteristics of vulnerable plaques (thin-cap atheroma), and absent from more stable plaques (fibroatheroma). It also demonstrates that thrombi associated with disrupted plaques contain appreciable numbers of MPO-positive cells.
22. Marsche G, Hammer A, Oskolkova O, et al.: Hypochlorite-modified high density lipoprotein, a high affinity ligand to scavenger receptor class B, type I, impairs high density lipoprotein-dependent selective lipid uptake and reverse cholesterol transport. J Biol Chem 2002, 277(35): 32172-32179.
23. Hazell LJ, Arnold L, Flowers D, et al.: Presence of hypochlorite-modified proteins in human atherosclerotic lesions. J Clin Invest 1996, 97(6): 1535-1544.
24. 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(9): 2075-2081.
25. Wang Z, Nicholls SJ, Rodriguez ER, et al.: Protein carbamylation links inflammation, smoking, uremia and atherogenesis. Nat Med 2007, 13(10): 1176-1184.
26. Eiserich JP, Baldus S, Brennan M-L, et al.: Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science 2002, 296(5577): 2391-2394.
27. 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. Arteriosclerosis, Thrombosis, and Vascular Biology 2004, 24(7): 1309-1314.
28. Fu X, Kassim SY, Parks WC, Heinecke JW: Hypochlorous acid oxygenates the cysteine switch domain of pro-matrilysin (MMP-7). A mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase. J Biol Chem 2001, 276(44): 41279-41287.
29. Zhang R, Brennan ML, Fu X, et al.: Association between myeloperoxidase levels and risk of coronary artery disease. JAMA 2001, 286(17): 2136-2142.
30. Brennan M-L, Penn MS, van Lente F, et al.: Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 2003, 349(17): 1595-1604.
31. • Meuwese MC, Stroes ESG, Hazen SL, 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(2): 159-165. This article shows that elevated MPO serum levels are predictive of future risk of CAD during an 8-year follow-up in apparently healthy individuals. This suggests that inflammatory activation, as detected by MPO secretion, precedes CAD onset by many years.
32. Wong ND, Gransar H, Narula J, et al.: Myeloperoxidase, subclinical atherosclerosis, and cardiovascular disease events. JACC Cardiovasc Imaging 2009, 2(9): 1093-1099.
33. Touzé E, Toussaint J-F, Coste J, et al.: Reproducibility of high-resolution MRI for the identification and the quantification of carotid atherosclerotic plaque components: consequences for prognosis studies and therapeutic trials. Stroke 2007, 38(6): 1812-1819.
34. Bogdanov A, Matuszewski L, Bremer C, et al.: Oligomerization of paramagnetic substrates result in signal amplification and can be used for MR imaging of molecular targets. Mol Imaging 2002, 1(1): 16-23.
35. Chen JW, Pham W, Weissleder R, Bogdanov A: Human myeloperoxidase: a potential target for molecular MR imaging in atherosclerosis. Magn Reson Med 2004, 52(5): 1021-1028.
36. Dunford HB, Hsuanyu Y: Kinetics of oxidation of serotonin by myeloperoxidase compounds I and II. Biochem Cell Biol 1999, 77(5): 449-457.
37. Querol M, Chen JW, Bogdanov AA: A paramagnetic contrast agent with myeloperoxidase-sensing properties. Org Biomol Chem 2006, 4(10): 1887-1895.
38. Querol M, Chen JW, Weissleder R, Bogdanov A: DTPA-bisamide-based MR sensor agents for peroxidase imaging. Org Lett 2005, 7(9): 1719-1722.
39. • Rodríguez E, Nilges M, Weissleder R, Chen JW: Activatable magnetic resonance imaging agents for myeloperoxidase sensing: mechanism of activation, stability, and toxicity. J Am Chem Soc 2010, 132(1): 168-177. This study details the mechanisms of activation, specificity, stability, and cytotoxicity characteristics of several MRI MPO probes, including MPO-Gd.
40. Chen JW, Querol Sans M, Bogdanov A, Weissleder R: Imaging of myeloperoxidase in mice by using novel amplifiable paramagnetic substrates. Radiology 2006, 240(2): 473-481.
41. •• Nahrendorf M, Sosnovik D, Chen JW, et al.: Activatable magnetic resonance imaging agent reports myeloperoxidase activity in healing infarcts and noninvasively detects the antiinflammatory effects of atorvastatin on ischemia-reperfusion injury. Circulation 2008, 117(9): 1153-1160. This is the first study showing the ability to image MPO activity using the MRI probe MPO-Gd in a mouse model of cardiovascular disease (myocardial ischemia-reperfusion injury). Furthermore, the anti-inflammatory effects of atorvastatin treatment were successfully tracked.
42. Chen JW, Breckwoldt MO, Aikawa E, Chiang G, Weissleder R: Myeloperoxidase-targeted imaging of active inflammatory lesions in murine experimental autoimmune encephalomyelitis. Brain 2008, 131(Pt 4): 1123-1133.
43. •• Breckwoldt MO, Chen JW, Stangenberg L, et al.: Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci USA 2008, 105(47): 18584-18589. This study showed that MPO-Gd can be used to track the temporal changes in inflammatory response and oxidative stress in a mouse model of stroke.
44. •• Ronald JA, Chen JW, Chen Y, et al.: Enzyme-sensitive magnetic resonance imaging targeting myeloperoxidase identifies active inflammation in experimental rabbit atherosclerotic plaques. Circulation 2009, 120(7): 592-599. This is currently the only study showing the ability to noninvasively detect MPO activity in an animal model of atherosclerosis in vivo. It required the combined use of a rabbit model of atherosclerosis, high-resolution MRI, and the activatable MRI probe, MPO-Gd.
45. Brennan ML, Anderson MM, Shih DM, et al.: Increased atherosclerosis in myeloperoxidase-deficient mice. J Clin Invest 2001, 107(4): 419-430.
46. Querol Sans M, Chen JW, Weissleder R, Bogdanov AA: Myeloperoxidase activity imaging using (67)Ga labeled substrate. Mol Imaging Biol 2005, 7(6): 403-410.
47. Li D, Patel AR, Klibanov AL, et al.: Molecular imaging of atherosclerotic plaques targeted to oxidized LDL receptor LOX-1 by SPECT/CT and magnetic resonance. Circ Cardiovasc Imaging 2010, 3(4): 464-472.
48. Silvera SS, Aidi HE, Rudd JHF, et al.: Multimodality imaging of atherosclerotic plaque activity and composition using FDG-PET/CT and MRI in carotid and femoral arteries. Atherosclerosis 2009, 207(1): 139-143.
49. •• Shepherd J, Hilderbrand SA, Waterman P, et al.: A fluorescent probe for the detection of myeloperoxidase activity in atherosclerosis-associated macrophages. Chem Biol 2007, 14(11): 1221-1231. This study describes the first in vivo imaging of MPO activity using an activatable fluorescent probe called SNAPF. Upon activation the agent emits far-red light, making it highly suitable for in vivo imaging.
50. Calfon MA, Vinegoni C, Ntziachristos V, Jaffer FA: Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques. J Biomed Opt 2010, 15(1): 011107.
51. •• Gross S, Gammon ST, Moss BL, et al.: Bioluminescence imaging of myeloperoxidase activity in vivo. Nat Med 2009, 15(4): 455-461. This study describes the use of the chemiluminescent agent luminol to locate MPO activity in vivo in a variety of mouse models using bioluminescence imaging. In vivo specificity of luminol oxidation (and thus luminescence) to MPO, but not eosinophil peroxidase, activity is also shown.