Serum MMP-9 Diagnostics, Prognostics, and Activation in Acute Coronary Syndrome and Its Recurrence

J Cardiovasc Transl Res. 2018 Jun;11(3):210-220. doi: 10.1007/s12265-018-9789-x. Epub 2018 Jan 18.

Abstract

Matrix metalloproteinase (MMP)-9 is crucial in atherosclerotic plaque rupture and tissue remodeling after a cardiac event. The balance between MMP-9 and endogenous inhibitor, tissue inhibitors of matrix metalloproteinase 1 (TIMP-1), is important in acute coronary syndrome (ACS). This is an age- and gender-matched case-control study of ACS (N = 669). Patients (45.7%) were resampled after recovery, and all were followed up for 6 years. The molecular forms of MMP-9 were investigated by gelatin zymography. Diagnostically, MMP-9 and the MMP-9/TIMP-1 molar ratio were associated with ACS (OR 5.81, 95% CI 2.65-12.76, and 4.96, 2.37-10.38). The MMP-9 concentrations decreased 49% during recovery (p < 0.001). The largest decrease of these biomarkers between acute and recovery phase (ΔMMP-9) protected the patients from major adverse cardiac events, especially the non-fatal events. The fatal events were associated with in vitro activatable MMP-9 levels (p = 0.028). Serum MMP-9 and the MMP-9/TIMP-1 molar ratio may be valuable in ACS diagnosis and prognosis. High serum MMP-9 activation potential is associated with poor cardiovascular outcome.

Keywords: Atherosclerosis; Cardiovascular diseases; Coronary artery disease; Inflammation; Plaque rupture; Serum biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / enzymology
  • Acute Coronary Syndrome / mortality
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Enzyme Activation
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / blood*
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Recurrence
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-1 / blood

Substances

  • Biomarkers
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • MMP9 protein, human
  • Matrix Metalloproteinase 9