Changes in plasma levels of MMP-9, MMP-7 and their inhibitors in patients with coronary artery disease

Rom J Intern Med. 2010;48(2):141-9.

Abstract

To describe the enzymatic profile of plasma matrix metalloproteinases (MMP-7 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in different categories of patients (pts.) with coronary artery disease (CAD), and their relationship with clinical status, left ventricular (LV) function and remodelling.

Methods: Total plasma MMP7, active fraction of MMP9, TIMP1 and TIMP2 were determined in 68 consecutive pts with confirmed CAD (Group A, 56.6 +/- 9 y, 75% men, LVEF 56.4 +/- 11%) and compared with a control group of 23 pts. without cardiovascular disease and normal coronary arteries (Group B, 58.1 +/- 10 y, 56.5% men, LVEF 58.7 +/- 5%). LVEF and wall motion index (WMI) were computed. Diastolic function parameters were evaluated: mitral E/A ratio, E/E'septal ratio. We calculated global longitudinal (L), circumferential (C) and radial (R) strain (S) and strain rate (SR) values as the average of segmental values, by 2D strain analysis.

Results: The active form of MMP9 differed significantly between group A and B, as did the MMP9/TIMP1 and MMP9/TIMP2 ratios (8.78 +/- 10.0 ng/ml vs 3.33 +/- 4.0 ng/ml; 5.43 +/- 3.4 vs 0.85 +/- 0.9, and 11.60 +/- 5.2 vs 3.71 +/- 1.0, respectively, p < 0.04 for all). Group A included 35 pts. with acute coronary syndromes (ACS) and 33 pts. with stable angina (SA), with similar profile of LVEF and number of coronary arteries involved. There were no significant differences in plasma MMP9, MMP9/TIMP1 and MMP/TIMP2 ratio between normal and SA group, but only between normal and ACS group (p = 0.02 for MMP9). In group A, only MMP7, TIMP1/MMP7 and TIMP2/MMP7 ratio correlated with markers of systolic function: LVEF, WMI and global LS.

Conclusion: There were no significant changes in extracellular matrix markers in pts. with chronic stable ischemia vs normals. Only active form of MMP9 and its ratio with TIMP differed significantly in ACS. Total MMP7 and its ratio with TIMP correlated with parameters of LV systolic function even in pts. with normal LVEF.

Publication types

  • Clinical Trial

MeSH terms

  • Acute Coronary Syndrome / etiology
  • Acute Coronary Syndrome / metabolism*
  • Aged
  • Chronic Disease
  • Coronary Angiography
  • Echocardiography
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Myocardial Ischemia / complications
  • Myocardial Ischemia / diagnosis
  • Myocardial Ischemia / metabolism*
  • Myocardial Ischemia / physiopathology
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / metabolism*
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Remodeling*

Substances

  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 9