Serum MMP-9 Diagnostics, Prognostics, and Activation in Acute Coronary Syndrome and Its Recurrence - PubMed (original) (raw)

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

Laura Lahdentausta et al. J Cardiovasc Transl Res. 2018 Jun.

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.

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Conflict of interest statement

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The study was conducted according to the Declaration of Helsinki. The ethical committee of the Lund University approved the study design. No animal studies were carried out by the authors for this article.

All participants provided informed consent.

Figures

Fig. 1

Fig. 1

Cumulative survival according to the serum MMP-9, MMP-9/TIMP-1, ΔMMP-9, and ΔMMP-9/TIMP-1 quartiles in ACS patients, endpoint event being MACE. MACE includes both fatal and non-fatal endpoints. ΔMMP-9 and ΔMMP-9/TIMP-1 refer to difference between acute and recovery phase (i.e., acute—recovery phase values). The survival was investigated by Cox regression model adjusted for age and sex

Fig. 2

Fig. 2

Gelatin zymography results. a Scatter plot of serum MMP-9 levels measured by ELISA and total MMP-9 intensities analyzed by gelatin zymography. The correlation coefficient and p value are shown. b Representative gelatin-zymography of ACS serum samples. Lane 1 is the molecular weight standard. Lanes 2, 4, and 6 are serum samples of patients with ACS without MMP-9 activating pretreatment. Lanes 3, 5, and 7 are the same serum samples, respectively, with 1 mM APMA pretreatment, which activates the pro-form of MMP-9. The gels are 10%, and the bands were visualized by Coomassie Brilliant Blue staining. Pro-MMP-2 bands are seen at 72 kDa. No proteolytically activated MMP-2 was observed (64 kDa)

Fig. 3

Fig. 3

Active and APMA-activatable MMP-9 analyzed by gelatin zymography presented as arbitrary units of intensities (Y1-axis) and corresponding MMP-9 concentrations measured by ELISA (Y2-axis) in the subjects selected for zymography. All measurement points are presented as dots, and group medians are presented with a line. Statistically significant differences are presented below the plot

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