Takazoe K, Ogawa H, Yasue H, Sakamoto T, Oshima S, Arai H, Moriyama Y, Shimomura H, Hirai N, Kaikita K, Soejima H, Misumi K, Hosoda K
Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto City, Japan.
Thromb Res. 1999 Jul 1;95(1):37-47. doi: 10.1016/s0049-3848(99)00020-1.
Protein C is one of the most important antithrombotic components. After activation by the thrombin-thrombomodulin complex on endothelial cells, activated protein C (APC) inactivates factors Va and VIIIa, which leads to the inhibition of thrombin formation. We examined the association of plasma levels of APC with the responsiveness to coronary thrombolytic therapy of the infarct-related coronary artery in patients with acute myocardial infarction (AMI). Plasma levels of APC, thrombin-antithrombin III complex (TAT), and plasminogen activator inhibitor (PAI) activity were measured in 32 consecutive AMI patients who underwent coronary angiography followed by thrombolytic therapy, and compared to the measurements in 23 control subjects. On admission, APC levels (ng/mL) were significantly elevated in patients with AMI, as compared with controls (2.5+/-0.4 vs. 1.2+/-0.2, 1.3+/-0.2, respectively, p<0.01). At discharge, plasma levels in AMI patients decline to values not significantly different from those in controls. (1.2+/-0.2, 1.3+/-0.2, respectively). TAT levels (ng/mL) were different among the groups in a fashion similar to that of APC (14.1+/-3.1 on admission vs. 3.3+/-0.4 at discharge, 1.8+/-0.1 in the control subjects, respectively, p<0.01). PAI activity levels (IU/mL) were higher on admission than at discharge and higher than the control subjects (19.7+/-1.8 vs. 10.5+/-1.0, 5.4 +/- 0.7, respectively, p<0.01). Thirty-two patients with AMI were classified into two groups according to the results of thrombolysis: the success group (24 patients) and the failure group (eight patients). APC levels were higher in the failure group than in the success group (5.1+/-0.7 vs. 1.6+/-0.2, p<0.01). TAT levels were also higher in the failure group than in the success group (30.8+/-9.6 vs. 8.6+/-1.7, p<0.01). PAI activity levels (IU/mL) were lower in the failure group than in the success group (13.5+/-3.1 vs. 21.7+/-2.1, p<0.05). There were correlations between APC and TAT levels both on admission (r=0.75, p<0.0001) and at discharge (r=0.71, p<0.0001). Elevated APC was thought to correlate with increased thrombin generation in patients with AMI. This study demonstrated that there was a significant relation between plasma APC level and the responsiveness to thrombolytic therapy of the infarct artery. This study may also indicate that increased thrombin generation is a cause of the resistance to thrombolytic therapy.
蛋白C是最重要的抗血栓形成成分之一。在内皮细胞上被凝血酶 - 血栓调节蛋白复合物激活后，活化蛋白C（APC）使因子Va和VIIIa失活，从而抑制凝血酶的形成。我们研究了急性心肌梗死（AMI）患者血浆中APC水平与梗死相关冠状动脉对冠状动脉溶栓治疗反应性之间的关联。对32例连续接受冠状动脉造影并随后进行溶栓治疗的AMI患者测定了血浆APC、凝血酶 - 抗凝血酶III复合物（TAT）和纤溶酶原激活物抑制剂（PAI）活性水平，并与23例对照受试者的测定结果进行比较。入院时，AMI患者的APC水平（ng/mL）与对照组相比显著升高（分别为2.5±0.4与1.2±0.2、1.3±0.2，p<0.01）。出院时，AMI患者的血浆水平下降至与对照组无显著差异的值（分别为1.2±0.2、1.3±0.2）。TAT水平（ng/mL）在各组之间的变化趋势与APC相似（入院时为14.1±3.1，出院时为3.3±0.4，对照组为1.8±0.1，p<0.01）。PAI活性水平（IU/mL）入院时高于出院时且高于对照组（分别为19.7±1.8与10.5±1.0、5.4±0.7，p<0.01）。根据溶栓结果，32例AMI患者被分为两组：成功组（24例）和失败组（8例）。失败组的APC水平高于成功组（5.1±0.7与1.6±0.2，p<0.01）。失败组的TAT水平也高于成功组（30.8±9.6与8.6±1.7，p<0.01）。PAI活性水平（IU/mL）失败组低于成功组（13.5±3.1与21.7±2.1，p<0.05）。入院时和出院时APC与TAT水平均存在相关性（r = 0.75，p<0.0001；r = 0.71，p<0.0001）。升高的APC被认为与AMI患者凝血酶生成增加相关。本研究表明血浆APC水平与梗死动脉对溶栓治疗的反应性之间存在显著关系。本研究还可能表明凝血酶生成增加是溶栓治疗抵抗的原因之一。
