Matrix metalloproteinase 9 polymorphism and outcome after myocardial infarction
AbstractMatrix metalloproteinase 9 (MMP9) is functionally implicated in the process of infarct healing. Several genetic variation of the MMP9 gene have been described, among which the MMP9 Arg668Gln polymorphism. In the present study, we assessed whether this polymorphism influences outcome after acute myocardial infarction (MI). One thousand forty-nine patients undergoing coronary angiography were genotyped for the MMP9 Arg668Gln polymorphism by TaqMan allelic discrimination assay. This population included 154 controls, 161 patients with non ST-elevation MI (NSTEMI), 504 patients with ST-elevation MI (STEMI), and 230 patients with angina. Frequency of the MMP9 Arg668Gln polymorphism in the global population was 25.1%, and was comparable between all groups. STEMI patients had higher creatine phosphokinase (CPK), troponin T (TnT) and MMP9 plasma levels and had lower ejection fraction (EF) than NSTEMI patients. However, the polymorphism was not associated with infarct severity as determined by peak CPK and TnT levels, nor with LV remodeling and outcome as assessed by 1-month EF and NYHA class, as well as 2- year mortality. In silico molecular modeling simulations predicted that the MMP9 polymorphism may decrease MMP9 activity, but this could not be verified by plasma determinations. This study investigated for the first time the association between the MMP9 Arg668Gln polymorphism and clinical outcome after acute MI. Our results indicate that the polymorphism does not seem to be associated with clinical outcome and in particular with the development of left ventricular dysfunction and heart failure.
Spinale FG. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 2007;87:1285-342.
Kai H, Ikeda H, Yasukawa H, et al. Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes. J Am Coll Cardiol 1998;32:368-72.
Lindsey M, Wedin K, Brown MD, et al. Matrix-dependent mechanism of neutrophil-mediated release and activation of matrix metalloproteinase 9 in myocardial ischemia/reperfusion. Circulation 2001;103:2181-7.
Squire IB, Evans J, Ng LL, et al. Plasma MMP-9 and MMP-2 following acute myocardial infarction in man: correlation with echocardiographic and neurohumoral parameters of left ventricular dysfunction. J Card Fail 2004;10:328-33.
Sundstrom J, Evans JC, Benjamin EJ, et al. Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: the Framingham Heart Study. Circulation 2004;109:2850-6.
Webb CS, Bonnema DD, Ahmed SH, et al. Specific temporal profile of matrix metalloproteinase release occurs in patients after myocardial infarction: relation to left ventricular remodeling. Circulation 2006;114:1020-7.
Wagner DR, Delagardelle C, Ernens I, et al. Matrix metalloproteinase-9 is a marker of heart failure after acute myocardial infarction. J Card Fail 2006;12:66-72.
Kelly D, Khan SQ, Thompson M, et al. Plasma tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9: novel indicators of left ventricular remodelling and prognosis after acute myocardial infarction. Eur Heart J 2008;29:2116-24.
Kelly D, Cockerill G, Ng LL, et al. Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: a prospective cohort study. Eur Heart J 2007;28:711-8.
Yan AT, Yan RT, Spinale FG, et al. Plasma matrix metalloproteinase-9 level is correlated with left ventricular volumes and ejection fraction in patients with heart failure. J Card Fail 2006;12:514-9.
Matsumura S, Oue N, Nakayama H, et al. A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer. J Cancer Res Clin Oncol 2005;131:19-25.
Hu Z, Huo X, Lu D, et al. Functional polymorphisms of matrix metalloproteinase-9 are associated with risk of occurrence and metastasis of lung cancer. Clin Cancer Res 2005;11:5433-9.
Jin G, Miao R, Hu Z, et al. Putative functional polymorphisms of MMP9 predict survival of NSCLC in a Chinese population. Int J Cancer 2009;124:2172-8.
Nan H, Niu T, Hunter DJ, Han J. Missense polymorphisms in matrix metalloproteinase genes and skin cancer risk. Cancer Epidemiol Biomarkers Prev 2008;17:3551-7.
Koh YS, Chang K, Kim PJ, et al. A close relationship between functional polymorphism in the promoter region of matrix metalloproteinase-9 and acute myocardial infarction. Int J Cardiol 2008;127:430-2.
Hlatky MA, Ashley E, Quertermous T, et al. Matrix metalloproteinase circulating levels, genetic polymorphisms, and susceptibility to acute myocardial infarction among patients with coronary artery disease. Am Heart J 2007;154:1043-51.
Kaplan RC, Smith NL, Zucker S, et al. Matrix metalloproteinase-3 (MMP3) and MMP9 genes and risk of myocardial infarction, ischemic stroke, and hemorrhagic stroke. Atherosclerosis 2008;201:130-7.
Murphy G, Knauper V. Relating matrix metalloproteinase structure to function: why the "hemopexin" domain? Matrix Biol 1997;15:511-8.
Wu S, Hsu LA, Teng MS, et al. Association of matrix metalloproteinase 9 genotypes and cardiovascular disease risk factors with serum matrix metalloproteinase 9 concentrations in Taiwanese individuals. Clin Chem Lab Med 2010;48:543-9.
Cha H, Kopetzki E, Huber R, et al. Structural basis of the adaptive molecular recognition by MMP9. J Mol Biol 2002;320:1065-79.
Gomis-Ruth FX, Maskos K, Betz M, et al. Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1. Nature 1997;389:77-81.
Eisenstein M, Shariv I, Koren G, et al. Modeling supra-molecular helices: extension of the molecular surface recognition algorithm and application to the protein coat of the tobacco mosaic virus. J Mol Biol 1997;266:135-43.
Katchalski-Katzir E, Shariv I, Eisenstein M, et al. Molecular surface recognition: determination of geometric fit between proteins and their ligands by correlation techniques. Proc Natl Acad Sci U S A 1992;89:2195-9.
Case DA, Darden TA, Cheatham TE, et al. Amber 8. San Francisco: University of California; 2004.
Roeb E, Schleinkofer K, Kernebeck T, et al. The matrix metalloproteinase 9 (mmp-9) hemopexin domain is a novel gelatin binding domain and acts as an antagonist. J Biol Chem 2002;277:50326-32.
Murphy G, Nagase H. Progress in matrix metalloproteinase research. Mol Aspects Med 2008;29:290-308.
Butler GS, Butler MJ, Atkinson SJ, et al. The TIMP2 membrane type 1 metalloproteinase "receptor" regulates the concentration and efficient activation of progelatinase A. A kinetic study. J Biol Chem 1998;273:871-80.
Lichte A, Kolkenbrock H, Tschesche H. The recombinant catalytic domain of membrane-type matrix metalloproteinase-1 (MT1-MMP) induces activation of progelatinase A and progelatinase A complexed with TIMP-2. FEBS Lett 1996;397:277-82.
- Abstract views: 1407
- PDF: 955
Copyright (c) 2011 Sophie Rodius, Guillermo Mulliert, Francisco Azuaje, Yvan Devaux, Daniel R. Wagner
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.