冠状动脉血栓中纤溶标志物的基因表达。
Gene expression of fibrinolytic markers in coronary thrombi.
作者信息
Nordeng Jostein, Solheim Svein, Åkra Sissel, Schandiz Hossein, Hoffmann Pavel, Roald Borghild, Bendz Bjørn, Arnesen Harald, Helseth Ragnhild, Seljeflot Ingebjørg
机构信息
Center for Clinical Heart Research, Oslo University Hospital Ullevål, Kirkeveien 166, Pb 4950 Nydalen, N-0424, Oslo, Norway.
Department of Cardiology, Oslo University Hospital Ullevål, Kirkeveien 166, Pb 4950 Nydalen, N-0424, Oslo, Norway.
出版信息
Thromb J. 2022 Apr 29;20(1):23. doi: 10.1186/s12959-022-00383-1.
BACKGROUND
The fibrinolytic system plays an important role in coronary artery atherothrombosis, and especially circulating plasminogen-activator inhibitor (PAI) type 1 (PAI-1) associates with increased mortality, infarct size and heart failure in patients with myocardial infarction (MI). In a cross-sectional study, we aimed to study whether genes encoding tissue plasminogen activator (tPA), urinary-type plasminogen activator (uPA), PAI-1 and PAI-2 are expressed in coronary thrombi from acute ST-elevation MI (STEMI) patients. Any relations to myocardial injury measured by peak troponin T, time from symptom onset to Percutaneous Coronary Intervention (PCI), and to different cell types present in the thrombi were also explored.
METHODS
Intracoronary thrombi were aspirated from 33 STEMI patients treated with primary PCI. The thrombi were snap-frozen for gene expression analyses, relatively quantified by RT PCR. Peripheral blood samples were drawn. Correlations were performed by Spearmans rho.
RESULTS
The genes were present in 74-94% of the thrombi. Median peak troponin T was 3434 μ/L and median ischemic time 152 min. There were no significant correlations between the measured genes and troponin T, or ischemic time. Genes encoding tPA, u-PA, PAI-1 and PAI-2 all correlated significantly to the presence of monocytes/macrophages (CD68) in the thrombi (p = 0.028, p < 0.001, p = 0.003, p < 0.001). PAI-1 and PAI-2 also correlated to endothelial cells (CD31) (p = 0.002, p = 0.016). uPA associated with neutrophil granulocytes (CD 66b) (p = 0.019).
CONCLUSION
Genes encoding tPA, uPA, PAI-1 and PAI-2 were highly expressed in human coronary thrombi from STEMI patients, indicating fibrinolytic regulators playing active roles in the thrombi, although not related to myocardial injury. All markers related to the presence of monocytes/macrophages, indicating connection to local inflammatory cells.
TRIAL REGISTRATION
The study is registered at clinicaltrials.gov with identification number NCT02746822 .
背景
纤维蛋白溶解系统在冠状动脉粥样硬化血栓形成中起重要作用，尤其是循环中的1型纤溶酶原激活物抑制剂（PAI-1）与心肌梗死（MI）患者的死亡率增加、梗死面积扩大及心力衰竭相关。在一项横断面研究中，我们旨在研究编码组织型纤溶酶原激活物（tPA）、尿激酶型纤溶酶原激活物（uPA）、PAI-1和PAI-2的基因是否在急性ST段抬高型心肌梗死（STEMI）患者的冠状动脉血栓中表达。还探讨了与通过肌钙蛋白T峰值测量的心肌损伤、症状发作至经皮冠状动脉介入治疗（PCI）的时间以及血栓中存在的不同细胞类型之间的任何关系。
方法
从33例接受直接PCI治疗的STEMI患者中抽吸冠状动脉血栓。将血栓速冻用于基因表达分析，通过逆转录聚合酶链反应（RT PCR）进行相对定量。采集外周血样本。采用Spearmans rho进行相关性分析。
结果
这些基因在74%至94%的血栓中存在。肌钙蛋白T峰值中位数为3434μ/L，缺血时间中位数为152分钟。所测基因与肌钙蛋白T或缺血时间之间无显著相关性。编码tPA、u-PA、PAI-1和PAI-2的基因均与血栓中单核细胞/巨噬细胞（CD68）的存在显著相关（p = 0.028，p < 0.001，p = 0.003，p < 0.001）。PAI-1和PAI-2也与内皮细胞（CD31）相关（p = 0.002，p = 0.016）。uPA与中性粒细胞（CD 66b）相关（p = 0.019）。
结论
编码tPA、uPA、PAI-1和PAI-2的基因在STEMI患者的人冠状动脉血栓中高表达，表明纤维蛋白溶解调节因子在血栓中发挥积极作用，尽管与心肌损伤无关。所有标志物均与单核细胞/巨噬细胞的存在相关，表明与局部炎症细胞有关。
试验注册
该研究已在clinicaltrials.gov注册，识别号为NCT02746822。
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