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Expression of matrix metalloproteinases-12 in ST-segment elevation myocardial infarction: A case-control study
Jing Wang1, Guoqing Wei, Wei Hu
1Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, P.R. China.
Abstract:
Matrix metalloproteinases-12 (MMP12) can lead to degradation of elastin resulting in plaque destabilization and rupture. MMP12 also facilitates platelet aggregation, adhesion, and granule secretion. However, evidence in the literature related to the function of MMP12 in ST-segment elevation myocardial infarction (STEMI) is little. This study investigated the expression of MMP12 in human coronary thrombus and examined the relationship between plasma MMP12 and STEMI.Arterial plasma was obtained from 46 STEMI patients and 52 stable angina pectoris (SAP) patients and 30 controls with angiographically normal coronary arteries. Coronary thrombi were obtained from 26 STEMI patients with a large thrombus burden (LTB). The expression levels of MMP12 in coronary thrombus were analyzed by immunohistochemistry and immunofluorescence, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and casein zymography. In addition, MMP12 concentration measured by enzyme-linked immunosorbent assay (ELISA) and activity measured by fluorescence resonance energy transfer (FRET) were used to assess the levels in plasma.We confirmed the expression of MMP12 in human coronary thrombus. MMP12 was secreted mainly in active form of 45 kDa in coronary thrombus. In plasma samples of the STEMI group, MMP12 concentrations were found to be higher than the SAP group (5.030 ± 2.24 pg/mL vs 3.010 ± 1.99 pg/mL, P < .05) but with lower MMP12 activity (332 ± 77 RFU vs 458 ± 91 RFU, P < .05). Also, the STEMI group demonstrated much higher MMP12 concentrations than the normal coronary artery control group (5.030 ± 2.24 pg/mL vs 1.720 ± 0.51 pg/mL, P < .05) and with lower MMP12 activity (332 ± 77 RFU vs 549 ± 112 RFU, P < .05). In addition, the STEMI group had significantly higher tissue inhibitor of metalloproteinases-1 (TIMP1) concentration (573.40 ± 270.60 pg/mL) than SAP group (384.50 ± 147.70 pg/mL) and control group (219.90 ± 154.80 pg/mL, P < .05). The imbalance in MMP12/TIMP ratio was observed in the STEMI group compared with SAP and control group (P < .05).This study demonstrated that MMP12 exists in human coronary thrombus. Patients with STEMI have elevated plasma level of MMP12 and the imbalance of MMP12/TIMP1. These data supported that MMP12 might be of potential relevance in STEMI.
Insights
Matrix metalloproteinases-12 (MMP12) is present in coronary thrombus and elevated in ST-segment elevation myocardial infarction (STEMI) patients. This suggests MMP12 plays a role in STEMI, potentially linked to an imbalance with tissue inhibitor of metalloproteinases-1 (TIMP1).
Area of Science:
- Cardiovascular Biology
- Biochemistry
- Molecular Medicine
Background:
- Matrix metalloproteinases-12 (MMP12) degrades elastin, destabilizing plaques and promoting rupture.
- MMP12 also influences platelet aggregation and secretion, relevant to thrombosis.
- Limited research exists on MMP12's specific role in ST-segment elevation myocardial infarction (STEMI).
Purpose of the Study:
- To investigate MMP12 expression in human coronary thrombus.
- To examine the relationship between plasma MMP12 levels and STEMI.
- To assess the balance between MMP12 and its inhibitor, TIMP1, in STEMI patients.
Main Methods:
- Coronary thrombi and arterial plasma were collected from STEMI patients, stable angina pectoris (SAP) patients, and healthy controls.
- MMP12 expression in thrombi was analyzed using immunohistochemistry, immunofluorescence, RT-PCR, Western blotting, and zymography.
- Plasma MMP12 concentration (ELISA) and activity (FRET), along with TIMP1 concentration, were measured.
Main Results:
- MMP12 was confirmed in human coronary thrombus, primarily as an active 45-kDa form.
- STEMI patients exhibited significantly higher plasma MMP12 concentrations compared to SAP patients and controls.
- Conversely, MMP12 activity was lower in STEMI patients, alongside elevated TIMP1 levels, indicating an MMP12/TIMP1 imbalance.
Conclusions:
- MMP12 is present and active within human coronary thrombus.
- Elevated plasma MMP12 concentrations and an altered MMP12/TIMP1 ratio are associated with STEMI.
- These findings highlight MMP12 as a potential biomarker and therapeutic target in STEMI.
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