Thromb Haemost 2012; 107(03): 409-416
DOI: 10.1160/TH11-10-0717
Review Article
Schattauer GmbH

Molecular imaging of matrix metalloproteinases in atherosclerotic plaques

Sébastien Lenglet
1   Cardiology Division, Foundation for Medical Research, Department of Medical Specialties, University of Geneva, Geneva, Switzerland
,
Aurélien Thomas
2   Department of Chemistry, Montréal University, Montréal, Québec, Canada
,
Pierre Chaurand
2   Department of Chemistry, Montréal University, Montréal, Québec, Canada
,
Katia Galan
1   Cardiology Division, Foundation for Medical Research, Department of Medical Specialties, University of Geneva, Geneva, Switzerland
,
François Mach
1   Cardiology Division, Foundation for Medical Research, Department of Medical Specialties, University of Geneva, Geneva, Switzerland
,
Fabrizio Montecucco
1   Cardiology Division, Foundation for Medical Research, Department of Medical Specialties, University of Geneva, Geneva, Switzerland
› Author Affiliations
Financial support: This research was funded by EU FP7, Grant number 201668, AtheroRemo to Dr. F. Mach. This work was also supported by the Swiss National Science Foundation Grants to Dr. F. Mach (#310030–118245) and Dr. Montecucco (#32002B-134963/1). This work was also funded by a grant from the Swiss Heart Foundation and Novartis Foundation to Dr. F. Mach. This work was funded by the “Sir Jules Thorn Trust Reg” fund and Gustave and Simone Prévot fund to Dr. F. Montecucco.
Further Information

Publication History

Received: 18 October 2011

Accepted after minor revision: 09 January 2011

Publication Date:
22 November 2017 (online)

Summary

Ischaemic stroke and myocardial infarction often result from the sudden rupture of an atherosclerotic plaque. The subsequent arterial thrombosis occluding the vessel lumen has been widely indicated as the crucial acute event causing peripheral tissue ischaemia. A complex cross-talk between systemic and intraplaque inflammatory mediators has been shown to regulate maturation, remodeling and final rupture of an atherosclerotic plaque. Matrix metalloproteinases (MMPs) are proteolytic enzymes (released by several cell subsets within atherosclerotic plaques), which favour atherogenesis and increase plaque vulnerability. Thus, the assessment of intraplaque levels and activity of MMP might be of pivotal relevance in the evaluation of the risk of rupture. New imaging approaches, focused on the visualisation of inflammation in the vessel wall and plaque, may emerge as tools for individualised risk assessment and prevention of events. In this review, we summarize experimental findings of the currently available invasive and noninvasive imaging techniques, used to detect the presence and activity of MMPs in atherosclerotic plaques.

 
  • References

  • 1 Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol 2006; 47: C7-12.
  • 2 Narula J, Garg P, Achenbach S. et al. Arithmetic of vulnerable plaques for non-invasive imaging. Nat Clin Pract Cardiovasc Med 2008; 05: S2-10.
  • 3 Montecucco F, Lenglet S, Gayet-Ageron A. et al. Systemic and intraplaque mediators of inflammation are increased in patients symptomatic for ischemic stroke. Stroke 2010; 41: 1394-1404.
  • 4 Aikawa M, Libby P. The vulnerable atherosclerotic plaque: pathogenesis and therapeutic approach. Cardiovasc Pathol 2004; 13: 125-138.
  • 5 Jacobsen JA, Major Jourden JL, Miller MT. et al. To bind zinc or not to bind zinc: an examination of innovative approaches to improved metalloproteinase inhibition. Biochim Biophys Acta 2010; 1803: 72-94.
  • 6 Nagase H, Woessner JF. Matrix metalloproteinases. J Biol Chem 1999; 274: 21491-21494.
  • 7 Newby AC. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev 2005; 85: 1-31.
  • 8 Baker AH, Edwards DR, Murphy G. Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci 2002; 115: 3719-3727.
  • 9 Baroncini VLA, Nakao LS, Ramos SG. et al. Assessment of MMP-9, TIMP-1, and COX-2 in normal tissue and in advanced symptomatic and asymptomatic carotid plaques. Thromb J 2011; 09: 6.
  • 10 Tanindi A, Sahinarslan A, Elbeg S. et al. Association of matrix metalloproteinase-1, matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1, and interleukin-6 with epicardial and myocardial perfusion. Coron Artery Dis 2011; 22: 253-258.
  • 11 Montecucco F, Di Marzo V, da Silva RF. et al. The activation of the cannabinoid receptor type 2 (CB2) reduces neutrophilic protease-mediated vulnerability in atherosclerotic plaques. Eur Heart J. 2011 epub ahead of print.
  • 12 Newby AC. Metalloproteinases and vulnerable atherosclerotic plaques. Trends Cardiovasc Med 2007; 17: 253-258.
  • 13 Halvorsen B, Otterdal K, Dahl TB. et al. Atherosclerotic plaque stability--what determines the fate of a plaque?. Prog Cardiovasc Dis 2008; 51: 183-194.
  • 14 Peeters W, Moll FL, Vink A. et al. Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome. Eur Heart J 2011; 32: 2314-2325.
  • 15 Busti C, Falcinelli E, Momi S. et al. Matrix metalloproteinases and peripheral arterial disease. Intern Emerg Med 2010; 05: 13-25.
  • 16 Lemaître V, O'Byrne TK, Borczuk AC. et al. ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis. J Clin Invest 2001; 107: 1227-1234.
  • 17 Kuzuya M, Nakamura K, Sasaki T. et al. Effect of MMP-2 deficiency on atherosclerotic lesion formation in apoE-deficient mice. Arterioscler Thromb Vasc Biol 2006; 26: 1120-1125.
  • 18 Johnson JL, George SJ, Newby AC. et al. Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries. Proc Natl Acad Sci USA 2005; 102: 15575-15580.
  • 19 Fu X, Kassim SY, Parks WC. et al. 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: 41279-41287.
  • 20 Halpert I, Sires UI, Roby JD. et al. Matrilysin is expressed by lipid-laden macro-phages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci USA 1996; 93: 9748-9753.
  • 21 Laxton RC, Hu Y, Duchene J. et al. A role of matrix metalloproteinase-8 in atherosclerosis. Circ Res 2009; 105: 921-929.
  • 22 Montero I, Orbe J, Varo N. et al. C-react ive pro te in induce s matr ix met all o proteinase-1 and -10 in human endothelial cells: implications for clinical and subclinical atherosclerosis. J Am Coll Cardiol 2006; 47: 1369-1378.
  • 23 Nakamura H, Fujii Y, Ohuchi E. et al. Activation of the precursor of human stromelysin 2 and its interactions with other matrix metalloproteinases. Eur J Biochem 1998; 253: 67-75.
  • 24 Schönbeck U, Mach F, Sukhova GK. et al. Expression of stromelysin-3 in atherosclerotic lesions: regulation via CD40-CD40 ligand signaling in vitro and in vivo. J Exp Med 1999; 189: 843-853.
  • 25 Liang J, Liu E, Yu Y. et al. Macrophage metalloelastase accelerates the progression of atherosclerosis in transgenic rabbits. Circulation 2006; 113: 1993-2001.
  • 26 Yu Y, Koike T, Kitajima S. et al. Temporal and quantitative analysis of expression of metalloproteinases (MMPs) and their endogenous inhibitors in atherosclerotic lesions. Histol Histopathol 2008; 23: 1503-1516.
  • 27 Deguchi JO, Aikawa E, Libby P. et al. Matrix metalloproteinase-13/collagenase-3 deletion promotes collagen accumulation and organization in mouse atherosclerotic plaques. Circulation 2005; 112: 2708-2715.
  • 28 Ray BK, Shakya A, Turk JR. et al. Induction of the MMP-14 gene in macrophages of the atherosclerotic plaque: role of SAF-1 in the induction process. Circ Res 2004; 95: 1082-1090.
  • 29 Schneider F, Sukhova GK, Aikawa M. et al. Matrix-metalloproteinase-14 deficiency in bone-marrow-derived cells promotes collagen accumulation in mouse atherosclerotic plaques. Circulation 2008; 117: 931-939.
  • 30 Uzui H, Harpf A, Liu M. et al. Increased expression of membrane type 3-matrix metalloproteinase in human atherosclerotic plaque: role of activated macrophages and inflammatory cytokines. Circulation 2002; 106: 3024-3030.
  • 31 Davies JR, Rudd JH, Weissberg PL. et al. Radionuclide imaging for the detection of inflammation in vulnerable plaques. J Am Coll Cardiol 2006; 47: 57-68.
  • 32 Fujimoto S, Hartung D, Ohshima S. et al. Molecular imaging of matrix metalloproteinase in atherosclerotic lesions: resolution with dietary modification and statin therapy. J Am Coll Cardiol 2008; 52: 1847-1857.
  • 33 Haider N, Hartung D, Fujimoto S. et al. Dual molecular imaging for targeting metalloproteinase activity and apoptosis in atherosclerosis: molecular imaging facilitates understanding of pathogenesis. J Nucl Cardiol 2009; 16: 753-762.
  • 34 Ohshima S, Petrov A, Fujimoto S. et al. Molecular imaging of matrix metalloproteinase expression in atherosclerotic plaques of mice deficient in apolipoprotein e or low-density-lipoprotein receptor. J Nucl Med 2009; 50: 612-617.
  • 35 Nakashima Y, Plump AS, Raines EW. et al. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb 1994; 14: 133-140.
  • 36 Ishibashi S, Herz J, Maeda N. et al. The two-receptor model of lipoprotein clearance: tests of the hypothesis in “knockout” mice lacking the low density lipoprotein receptor, apolipoprotein E, or both proteins. Proc Natl Acad Sci USA 1994; 91: 4431-4435.
  • 37 Calara F, Silvestre M, Casanada F. et al. Spontaneous plaque rupture and secondary thrombosis in apolipoprotein E-deficient and LDL receptor-deficient mice. J Pathol 2001; 195: 257-263.
  • 38 Jackson CL, Bennett MR, Biessen EA. et al. Assessment of unstable atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2007; 27: 714-720.
  • 39 Kuge Y, Takai N, Ishino S. et al. Distribution profiles of membrane Type-1 matrix metalloproteinase (MT1-MMP), matrix metalloproteinase-2 (MMP-2) and cyclooxygenase-2 (COX-2) in rabbit atherosclerosis: comparison with plaque instability analysis. Biol Pharm Bull 2007; 30: 1634-1640.
  • 40 Rajavashisth TB, Xu XP, Jovinge S. et al. Membrane type 1 matrix metalloproteinase expression in human atherosclerotic plaques: evidence for activation by proinflammatory mediators. Circulation 1999; 99: 3103-3109.
  • 41 Kuge Y, Takai N, Ogawa Y. et al. Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques. Eur J Nucl Med Mol Imaging 2010; 37: 2093-2104.
  • 42 Stary HC, Chandler AB, Glagov S. et al. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the committee on vascular lesions of the council on arteriosclerosis, American Heart Association. Circulation 1994; 89: 2462-2478.
  • 43 Stary HC, Chandler AB, Dinsmore RE. et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the committee on vascular lesions of the Council on arteriosclerosis, American Heart Association. Circulation 1995; 92: 1355-1374.
  • 44 Shiomi M, Ito T, Hirouchi Y. et al. Stability of atheromatous plaque affected by lesional composition: study of WHHL rabbits treated with statins. Ann NY Acad Sci 2001; 947: 419-423.
  • 45 Razavian M, Tavakoli S, Zhang J. et al. Atherosclerosis Plaque Heterogeneity and Response to Therapy Detected by In Vivo Molecular Imaging of Matrix Metalloproteinase Activation. J Nucl Med 2011; 52: 1795-1802.
  • 46 Weissleder R, Ntziachristos V. Shedding light onto live molecular targets. Nat Med 2003; 09: 123-128.
  • 47 Ntziachristos V, Ripoll J, Wang LV. et al. Looking and listening to light: the evolution of whole-body photonic imaging. Nat Biotechnol 2005; 23: 313-320.
  • 48 Deguchi JO, Aikawa M, Tung CH. et al. Inflammation in atherosclerosis: visualizing matrix metalloproteinase action in macrophages in vivo. Circulation 2006; 114: 55-62.
  • 49 Chen J, Tung CH, Allport JR. et al. Nearinfrared fluorescent imaging of matrix metalloproteinase activity after myocardial infarction. Circulation 2005; 111: 1800-1805.
  • 50 Wallis de Vries BM, Hillebrands JL, van Dam GM. et al. Images in cardiovascular medicine. Multispectral nearinfrared fluorescence molecular imaging of matrix metalloproteinases in a human carotid plaque using a matrix-degrading metalloproteinase-sensitive activatable fluorescent probe. Circulation 2009; 119: 534-536.
  • 51 Kim DE, Kim JY, Schellingerhout D. et al. Protease imaging of human atheromata captures molecular information of atherosclerosis, complementing anatomic imaging. Arterioscler Thromb Vasc Biol 2010; 30: 449-456.
  • 52 Razansky D, Harlaar NJ, Hillebrands JL. et al. Multispectral optoacoustic tomography of matrix metalloproteinase activity in vulnerable human carotid plaques. Mol Imaging Biol. 2011 epub ahead of print.
  • 53 Razansky D, Vinegoni C, Ntziachristos V. Multispectral photoacoustic imaging of fluorochromes in small animals. Opt Lett 2007; 32: 2891-2893.
  • 54 Ma R, Taruttis A, Ntziachristos V. et al. Multispectral optoacoustic tomography (MSOT) scanner for whole-body small animal imaging. Opt Express 2009; 17: 21414-21426.
  • 55 Sanz J, Fayad ZA. Imaging of atherosclerotic cardiovascular disease. Nature 2008; 451: 953-957.
  • 56 Cai JM, Hatsukami TS, Ferguson MS. et al. Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation 2002; 106: 1368-1373.
  • 57 Lancelot E, Amirbekian V, Brigger I. et al. Evaluation of matrix metalloproteinases in atherosclerosis using a novel noninvasive imaging approach. Arterioscler Thromb Vasc Biol 2008; 28: 425-432.
  • 58 Amirbekian V, Aguinaldo JG, Amirbekian S. et al. Atherosclerosis and matrix metalloproteinases: experimental molecular MR imaging in vivo. Radiology 2009; 251: 429-438.
  • 59 Phipps JE, Hatami N, Galis ZS. et al. A fluorescence lifetime spectroscopy study of matrix metalloproteinases-2 and -9 in human atherosclerotic plaque. J Biophotonics 2011; 04: 650-658.
  • 60 Marcu L, Jo JA, Fang Q. et al. Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy. Atherosclerosis 2009; 204: 156-164.
  • 61 Stephens DN, Park J, Sun Y. et al. Intraluminal fluorescence spectroscopy catheter with ultrasound guidance. J Biomed Opt 2009; 14 030505 1-3.
  • 62 Chaurand P, Schwartz SA, Reyzer ML. et al. Imaging mass spectrometry: principles and potentials. Toxicol Pathol 2005; 33: 92-101.
  • 63 Cornett DS, Reyzer ML, Chaurand P. et al. MALDI imaging mass spectrometry: molecular snapshots of biochemical systems. Nat Methods 2007; 04: 828-833.
  • 64 Franck J, Arafah K, Elayed M. et al. MALDI imaging mass spectrometry: state of the art technology in clinical proteomics. Mol Cell Proteomics 2009; 08: 2023-2033.
  • 65 Chaurand P, Schwartz SA, Billheimer D. et al. Integrating histology and imaging mass spectrometry. Anal Chem 2004; 76: 1145-1155.
  • 66 Schwamborn K, Caprioli RM. Molecular imaging by mass spectrometry-looking beyond classical histology. Nat Rev Cancer 2010; 10: 639-646.
  • 67 Chaurand P, Sanders ME, Jensen RA. et al. Proteomics in diagnostic pathology: profiling and imaging proteins directly in tissue sections. Am J Pathol 2004; 165: 1057-1068.
  • 68 Thomas A, Lenglet S, Chaurand P. et al. Mass spectrometry for the evaluation of cardiovascular diseases based on proteomics and lipidomics. Thromb Haemost 2011; 106: 20-33.
  • 69 Muruganantham S, Liyanage R, Lay Jr JO. et al. Towards visualizing the spatial localization of matrix metalloproteinases (MMPs) activity during the foreign body response (FBR) using MALDI-TOF MS imaging. 59th ASMS conference on Mass Spectrometry, 5-9 June 2011. Available at: https://www.asms.org/Home/tabid/36/Default.aspx
  • 70 Dobrucki LW, Sinusas AJ. PET and SPECT in cardiovascular molecular imaging. Nat Rev Cardiol 2010; 07: 38-47.
  • 71 Yuan C, Kerwin WS, Yarnykh VL. et al. MRI of atherosclerosis in clinical trials. NMR Biomed 2006; 19: 636-654.
  • 72 Balu N, Wang J, Dong L. et al. Current techniques for MR imaging of atherosclerosis. Top Magn Reson Imaging 2009; 20: 203-215.
  • 73 Ntziachristos V, Bremer C, Weissleder R. Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur Radiol 2003; 13: 195-208.
  • 74 Chang K, Jaffer F. Advances in fluorescence imaging of the cardiovascular system. J Nucl Cardiol 2008; 15: 417-428.
  • 75 Chang K, Francis SA, Aikawa E. et al. Pioglitazone suppresses inflammation in vivo in murine carotid atherosclerosis: novel detection by dual-target fluorescence molecular imaging. Arterioscler Thromb Vasc Biol 2010; 30: 1933-1939.
  • 76 Shon SM, Park JH, Nahrendorf M. et al. Exercise attenuates matrix metalloproteinase activity in preexisting atherosclerotic plaque. Atherosclerosis 2011; 216: 67-73.
  • 77 Kubota K, Kita J, Shimoda M. et al. Intraoperative assessment of reconstructed vessels in living-donor liver transplantation, using a novel fluorescence imaging technique. J Hepatobiliary Pancreat Surg 2006; 13: 100-104.
  • 78 Dzurinko VL, Gurwood AS, Price JR. Intravenous and indocyanine green angiography. Optometry 2004; 75: 743-755.
  • 79 Jaffer FA, Vinegoni C, John MC. et al. Real-time catheter molecular sensing of inflammation in proteolytically active atherosclerosis. Circulation 2008; 118: 1802-1809.