Aab Cardiovascular Research Institute, University of Rochester School of Medicine, Rochester, New York.
Department of Medicine, Division of Cardiology, University of Rochester School of Medicine, Rochester, New York.
Transl Res. 2018 May;195:1-12. doi: 10.1016/j.trsl.2017.11.006. Epub 2017 Dec 2.
It is assumed that platelets in diseased conditions share similar properties to platelets in healthy conditions, although this has never been examined in detail for myocardial infarction (MI). We examined platelets from patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) compared with platelets from healthy volunteers to evaluate for differences in platelet phenotype and function. Platelet activation was examined and postreceptor signal transduction pathways were assessed. Platelet-derived plasma biomarkers were evaluated by receiver operator characteristic curve analysis. Maximum platelet activation through the thromboxane receptor was greater in STEMI than in NSTEMI but less through protease-activated receptor 1. Extracellular-signal related-kinase 5 activation, which can activate platelets, was increased in platelets from subjects with STEMI and especially in platelets from patients with NSTEMI. Matrix metalloproteinase 9 (MMP9) protein content and enzymatic activity were several-fold greater in platelets with MI than in control. Mean plasma MMP9 concentration in patients with MI distinguished between STEMI and NSTEMI (area under curve [AUC] 75% [confidence interval (CI) 60-91], P = 0.006) which was superior to troponin T (AUC 66% [CI 48-85, P = 0.08), predicting STEMI with 80% sensitivity (95% CI 56-94), 90% specificity (CI 68-99), 70% AUC (CI 54-86, P < 0.0001), and NSTEMI with 50% sensitivity (CI 27-70), 90% specificity (CI 68-99), 70% AUC (CI 54-86, P = 0.03). Platelets from patients with STEMI and NSTEMI show differences in platelet surface receptor activation and postreceptor signal transduction, suggesting the healthy platelet phenotype in which antiplatelet agents are often evaluated in preclinical studies is different from platelets in patients with MI.
据假设，病变状态下的血小板与健康状态下的血小板具有相似的特性，尽管这一点从未在心肌梗死（MI）方面进行过详细研究。我们检测了 ST 段抬高型心肌梗死（STEMI）和非 ST 段抬高型心肌梗死（NSTEMI）患者的血小板与健康志愿者的血小板，以评估血小板表型和功能的差异。检测了血小板的激活情况，并评估了受体后信号转导途径。通过接收者操作特征曲线分析评估了血小板衍生的血浆生物标志物。通过血栓素受体，STEMI 患者的血小板激活程度大于 NSTEMI 患者，而通过蛋白酶激活受体 1 的激活程度则较低。可激活血小板的细胞外信号相关激酶 5 的激活在 STEMI 患者的血小板中增加，在 NSTEMI 患者的血小板中尤其增加。与对照相比，患有 MI 的血小板中的基质金属蛋白酶 9（MMP9）蛋白含量和酶活性高几倍。MI 患者的平均血浆 MMP9 浓度可区分 STEMI 和 NSTEMI（曲线下面积 [AUC] 75% [置信区间（CI）60-91]，P = 0.006），优于肌钙蛋白 T（AUC 66% [CI 48-85，P = 0.08），以 80%的敏感性（95% CI 56-94）、90%的特异性（CI 68-99）、70%AUC（CI 54-86，P < 0.0001）预测 STEMI，以 50%的敏感性（CI 27-70）、90%的特异性（CI 68-99）、70%AUC（CI 54-86，P = 0.03）预测 NSTEMI。STEMI 和 NSTEMI 患者的血小板在血小板表面受体激活和受体后信号转导方面存在差异，这表明在临床前研究中经常评估抗血小板药物的健康血小板表型与 MI 患者的血小板不同。
