Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina.
Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina.
复制标题
不稳定型心绞痛中体循环中单核细胞激活呈时间依赖性的证据，但在急性心肌梗塞或稳定型心绞痛中则不然。
DOI：
10.1161/01.cir.90.4.1662
复制
发表时间：
1994
期刊：
影响因子：
37.8
通讯作者：
Philippe Asseman
中科院分区：
文献类型：
--
作者：
Brigitte Jude;Benaissa Agraou;Eugene P. McFadden;Sophie Susen;Christophe Bauters;P. Lepelley;C. Vanhaesbroucke;Patrick Devos;Alain Cosson;Philippe Asseman
背景
血小板活化在急性冠状动脉疾病的发病机制中起着关键作用。单核细胞参与动脉粥样硬化的进展，并且通过其合成组织因子（TF）的能力而成为血液凝固的有效活化剂。本研究的目的是比较不稳定型心绞痛、急性心肌梗死和稳定型心绞痛患者的外周血单核细胞和凝血激活标志物。
方法和结果
我们研究了26例不稳定型心绞痛患者（最后一次疼痛发作后10 +/- 5小时）、18例急性心肌梗死患者（疼痛发作后5 +/- 4小时）和34例稳定型心绞痛患者。我们测量了外周血单个核细胞（通过梯度离心分离并孵育16小时，有或无内毒素刺激）中TF表达水平、血浆凝血酶原片段1 + 2（F1 + 2）水平和外周血中纤维蛋白原水平。在不稳定型心绞痛患者中，刺激和未刺激的细胞均表现出比稳定型心绞痛患者更高水平的TF表达（P = .0001）。在急性心肌梗死患者中，单核细胞TF活性与稳定型心绞痛患者无差异。两组间F1 + 2和纤维蛋白原的平均水平无显著差异。仅在不稳定型心绞痛组中，纤维蛋白原（r = 0.72，P = 0.005）和F1 + 2（r = 0.54，P = 0.001）水平与单核细胞TF表达程度之间存在适度相关性。在不稳定型心绞痛患者中，单核细胞TF表达（刺激和未刺激，通过生物活性和抗原技术评估）和纤维蛋白原水平与最近一次疼痛发作开始的时间相关（.61 < r < .72，.02 < P < .0001）。相比之下，这些变量与急性心肌梗死患者疼痛发作的时间之间没有相关性。
结论
不稳定型心绞痛患者的全身单核细胞活化呈时间依赖性，纤维蛋白原水平呈时间依赖性升高，而心肌梗死患者则无此现象。这些发现提供了进一步的证据表明，一个特定的炎症过程发生在不稳定型心绞痛。需要进一步的研究来确定单核细胞活化是否是不稳定型心绞痛患者斑块不稳定的原因或结果，并澄清在这些情况下血小板和单核细胞活化之间的相互关系。
BACKGROUND
Platelet activation plays a pivotal role in the pathogenesis of acute coronary disease. Monocytes are involved in the progression of atherosclerosis and are potent activators of blood coagulation through their ability to synthesize tissue factor (TF). The aim of this study was to compare markers of monocyte and coagulation activation in the systemic blood of patients with unstable angina, acute myocardial infarction, or stable angina.
METHODS AND RESULTS
We studied 26 patients with unstable angina (10 +/- 5 hours after the onset of the last episode of pain), 18 patients with acute myocardial infarction (5 +/- 4 hours after the onset of pain), and 34 patients with stable angina. We measured levels of TF expression in peripheral blood mononuclear cells (isolated by gradient centrifugation and incubated for 16 hours, with or without endotoxin stimulation), levels of plasma prothrombin fragment 1 + 2 (F1 + 2), and levels of fibrinogen in peripheral blood. In patients with unstable angina, both stimulated and unstimulated cells exhibited higher levels of TF expression than in patients with stable angina (P = .0001). In patients with acute myocardial infarction, monocyte TF activity did not differ from that in patients with stable angina. Mean levels of F1 + 2 and of fibrinogen did not differ significantly between groups. Only in the unstable angina group, a modest correlation was found between fibrinogen (r = .72, P = .005) and F1 + 2 levels (r = .54, P = .001) levels and the degree of monocyte TF expression. In patients with unstable angina, monocyte TF expression (both stimulated and unstimulated, assessed by biological activity and by antigen techniques) and fibrinogen levels were correlated with the time elapsed from the beginning of the most recent episode of pain (.61 < r < .72, .02 < P < .0001). By contrast, there was no correlation between these variables and the time from onset of pain in patients with acute myocardial infarction.
CONCLUSIONS
A time-dependent activation of systemic monocytes and a time-dependent increase in fibrinogen levels occurs in unstable angina but not in myocardial infarction. These findings provide further evidence that a specific inflammatory process occurs in unstable angina. Further studies are required to determine whether monocyte activation is a cause or a consequence of plaque instability in patients with unstable angina and to clarify the interrelations between platelet and monocyte activation in these circumstances.