Wang Jing, Wei Guoqing, Hu Wei, Li Linhua, Ye Yujia, Wang Huawei, Wan Wen, Li Rui, Li Longjun, Ma Linling, Meng Zhaohui
Laboratory of Molecular Cardiology, Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, P.R. China.
Medicine (Baltimore). 2017 Oct;96(40):e8035. doi: 10.1097/MD.0000000000008035.
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.
基质金属蛋白酶-12（MMP12）可导致弹性蛋白降解，从而致使斑块不稳定和破裂。MMP12还能促进血小板聚集、黏附及颗粒分泌。然而，文献中关于MMP12在ST段抬高型心肌梗死（STEMI）中功能的证据较少。本研究调查了MMP12在人冠状动脉血栓中的表达，并探讨了血浆MMP12与STEMI之间的关系。
从46例STEMI患者、52例稳定型心绞痛（SAP）患者以及30例冠状动脉造影正常的对照者中获取动脉血浆。从26例血栓负荷较大（LTB）的STEMI患者中获取冠状动脉血栓。通过免疫组织化学、免疫荧光、逆转录-聚合酶链反应（RT-PCR）、蛋白质印迹法（WB）和酪蛋白酶谱法分析冠状动脉血栓中MMP12的表达水平。此外，采用酶联免疫吸附测定（ELISA）法测定MMP12浓度，并用荧光共振能量转移（FRET）法测定活性，以评估血浆中的水平。
我们证实了MMP12在人冠状动脉血栓中的表达。冠状动脉血栓中MMP12主要以45 kDa的活性形式分泌。在STEMI组血浆样本中，发现MMP12浓度高于SAP组（5.030±2.24 pg/mL对3.010±1.99 pg/mL，P<.05），但MMP12活性较低（332±77 RFU对458±91 RFU，P<.值）。此外，STEMI组的MMP12浓度也显著高于冠状动脉正常对照组（5.030±2.24 pg/mL对1.720±0.51 pg/mL，P<.05），且MMP12活性较低（332±77 RFU对549±112 RFU，P<.05）。另外，STEMI组金属蛋白酶组织抑制剂-1（TIMP1）浓度（573.40±270.60 pg/mL）显著高于SAP组（384.50±147.70 pg/mL）和对照组（219.90±154.80 pg/mL，P<.05）。与SAP组和对照组相比，STEMI组中观察到MMP12/TIMP比值失衡（P<.05）。
本研究表明，MMP12存在于人冠状动脉血栓中。STEMI患者血浆MMP水平升高且MMP12/TIMP1失衡。这些数据支持MMP12可能与STEMI具有潜在相关性。
