Plasma MMP-9 and MMP-2 following acute myocardial infarction in man: correlation with echocardiographic and neurohumoral parameters of left ventricular dysfunction.

BACKGROUND Left ventricular dilatation and elevated plasma natriuretic peptide levels predict adverse prognosis and the development of congestive heart failure after myocardial infarction. Altered matrix metalloproteinase (MMP) activity has been implicated in the structural changes associated with development of heart failure after myocardial injury. The aims of this study were to investigate plasma MMP-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 concentrations following acute myocardial infarction and their relationships with measures of left ventricular function. METHODS AND RESULTS Plasma MMP-2, MMP-9, TIMP-1, and N-terminal proBNP (N-BNP) were quantified on 5 consecutive days in 60 patients with acute myocardial infarction (39 anterior). N-BNP was measured on day 3. Echocardiographic assessment of left ventricular wall motion index and volumes was performed during admission and 6 weeks later. Plasma MMP-9 showed peaks on days 1 and 4. MMP-2 levels, similar on each day, were higher after inferior myocardial infarction. Plasma MMP-2 showed strong, inverse correlation with left ventricular volumes during and after admission. Plasma MMP-9 correlated directly with N-BNP (P=.022) and inversely with wall motion index during admission (P=.05). TIMP-1 levels were higher after anterior (1269, 870-1466 ng/mL) compared with inferior (1183, 856-1419 ng/mL, P=.05) acute myocardial infarction and fell from day 1 through 5 (P <.0005). CONCLUSION Plasma MMP-9 concentration correlates with neurohormonal and echocardiographic measures of left ventricular dysfunction after myocardial infarction. Higher left ventricular volumes are associated with lower plasma MMP-2 concentrations. Circulating MMP concentrations may provide insights into left ventricular remodeling after acute myocardial infarction.

[1]  L. Ng,et al.  An immunoluminometric assay for N-terminal pro-brain natriuretic peptide: development of a test for left ventricular dysfunction , 1999 .

[2]  S. Hamada,et al.  Sustained elevation of plasma brain natriuretic peptide levels associated with progressive ventricular remodelling after acute myocardial infarction. , 1999, Clinical science.

[3]  E. Ohlstein,et al.  Matrix metalloproteinase expression in cardiac myocytes following myocardial infarction in the rabbit. , 2001, Life sciences.

[4]  A. Takeshita,et al.  Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction. , 2003, American journal of physiology. Heart and circulatory physiology.

[5]  P. Libby,et al.  Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice. , 1999, Circulation.

[6]  J. Bryant,et al.  Evolution of matrix metalloprotease and tissue inhibitor expression during heart failure progression in the infarcted rat. , 2000, Cardiovascular research.

[7]  F. Cambien,et al.  Plasma Concentrations and Genetic Variation of Matrix Metalloproteinase 9 and Prognosis of Patients With Cardiovascular Disease , 2003, Circulation.

[8]  J. Dyck,et al.  Intracellular Action of Matrix Metalloproteinase-2 Accounts for Acute Myocardial Ischemia and Reperfusion Injury , 2002, Circulation.

[9]  J. Fleiss,et al.  Risk stratification and survival after myocardial infarction. , 1983, The New England journal of medicine.

[10]  S. Kusachi,et al.  Time dependent alterations of serum matrix metalloproteinase-1 and metalloproteinase-1 tissue inhibitor after successful reperfusion of acute myocardial infarction. , 1997, Heart.

[11]  A. Naylor,et al.  Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption. , 2000, Stroke.

[12]  H. Ishizaka,et al.  Plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 are increased in the coronary circulation in patients with acute coronary syndrome. , 2001, American heart journal.

[13]  P. Libby,et al.  Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. , 2000, The Journal of clinical investigation.

[14]  R. Sayers,et al.  Pathogenesis of abdominal aortic aneurysms--cellular and biochemical mechanisms. , 1996, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[15]  Richard T. Lee,et al.  Selective Matrix Metalloproteinase Inhibition Reduces Left Ventricular Remodeling but Does Not Inhibit Angiogenesis After Myocardial Infarction , 2002, Circulation.

[16]  T. Ueno,et al.  Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes. , 1998, Journal of the American College of Cardiology.

[17]  M. Zile,et al.  Matrix metalloproteinase inhibition during the development of congestive heart failure : effects on left ventricular dimensions and function. , 1999, Circulation research.

[18]  J. Berning,et al.  Early estimation of risk by echocardiographic determination of wall motion index in an unselected population with acute myocardial infarction. , 1990, The American journal of cardiology.

[19]  R M Whitlock,et al.  Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. , 1987, Circulation.

[20]  A. Luttun,et al.  Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure , 1999, Nature Medicine.

[21]  M. Radomski,et al.  Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart. , 2000, Circulation.

[22]  C. Frampton,et al.  Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction. , 1998, Circulation.

[23]  D. Barnett,et al.  Profile of plasma N-terminal proBNP following acute myocardial infarction; correlation with left ventricular systolic dysfunction. , 2000, European heart journal.