Matrix metalloproteinases and the activity of their tissue inhibitors in patients with ST-elevation myocardial infarction treated with primary angioplasty

Background: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in heart remodelling after acute myocardial infarction (MI). Their activity is connected with outcome and heart failure development. There is little data on MMP and TIMP activity changes in the setting of ST elevation MI (STEMI) treated with primary percutaneous coronary intervention (pPCI). Aim: To assess the dynamics of activity of MMP-2 and MMP-9 and their endogenous inhibitors TIMP-1 and TIMP-2 in the course of invasive treatment of STEMI. Methods: The study included 95 patients (age 61.8 ± 12.4 years; 35 women) treated with pPCI with stent implantation due to 100% closure of the target vessel in a setting of STEMI. We measured the activity of MMP-2 and MMP-9 (by zymography, expressed with arbitrary units, AU), CK-MB (U/L), troponin I (ng/mL), TIMP-1, TIMP-2 (ng/mL) concentrations in a peripheral blood before the pPCI, immediately after and 3, 6, 12, 24 and 48 h after the procedure. Left ventricular ejection fraction (LVEF) was estimated at the hospital discharge using the Simpson method. There were two control groups: 15 healthy persons and 15 patients with stable coronary artery disease matched for age and sex with the studied group. Results: The abrupt opening of the target vessel did not produce an early increase in the activity of the MMPs. Their activity was high at the beginning and slowly lowered with time after pPCI so that at 12, 24 and 48 h after pPCI their activity was significantly lower than before and immediately after the pPCI (p <0.05 for all comparisons). The abrupt opening of the target vessel did not produce significant changes in the TIMP concentration. Only the TIMP-1 showed a slow increase in concentration and achieved a significantly higher level 48 h after the procedure compared to its concentration before and immediately after pPCI (p <0.05). In 14 patients (15% of the studied group), the post procedure TIMI flow was estimated as lower than 3 (TIMI 1 or 2). There was significantly higher MMP-9 activity in this group before, immediately after and up to 3 h after PCI compared to the group with good angiographic effect (TIMI = 3 after procedure). Patients with lowered LVEF (<50%) at hospital discharge had higher MMP-9 activity immediately after and 3 h after pPCI compared to patients with preserved LVEF. The same relation was observed for TIMP-2 level, where patients with a higher level before and immediately after pPCI had lowered LVEF at discharge. Conclusions: 1. The activity level of MMP-2 and MMP-9 is elevated during the STEMI acute phase and falls 12 h after successful pPCI, while TIMP-1 concentration only rises 48 h after the procedure. 2. The abrupt opening of the target vessel in STEMI does not produce acute changes in MMP-2, MMP-9 activity or TIMP-1 and TIMP-2 concentration. 3. The 'no-reflow' phenomenon in STEMI patients occurs more often in those with higher MMP-9 activity before pPCI. 4. Lowered LVEF at hospital discharge is observed in patients with higher periprocedural MMP-9 activity and TIMP-2 level.