Laboratory of Atherosclerosis, Division of Cardiovascular Sciences, CIMA-University of Navarra, Pamplona, Spain.
J Thromb Haemost. 2013 Aug;11(8):1464-73. doi: 10.1111/jth.12312.
Matrix metalloproteinases (MMPs) mediate tissue injury during stroke but also neurovascular remodeling and we have shown that MMP-10 is involved in atherothrombosis.
The purpose of this study was to examine the relationship between proMMP-10 and clinical outcome, assessing inflammatory and proteolytic markers, in patients with acute ischemic stroke.
We prospectively studied 76 patients with ischemic stroke treated with tPA within the first 3 h from symptom onset, compared with 202 non-tPA-treated ischemic stroke patients and 83 asymptomatic subjects. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Hemorrhagic transformation (HT) and severe brain edema were diagnosed by cranial CT. Good functional outcome was defined as a modified Rankin scale score ≤ 2 at 90 days. Serum levels of MMP-9, proMMP-10, TIMP-1, tumor necrosis factor-α (TNFα), interleukin-6 and cellular fibronectin were measured at admission. The effect of TNFα on endothelial proMMP-10 was assessed in vitro.
Serum proMMP-10 concentration in ischemic stroke patients, non-treated or treated with t-PA, which was higher than age-matched healthy subjects (P < 0.0001), was independently associated with higher infarct volume, severe brain edema, neurological deterioration and poor functional outcome at 3 months (all P < 0.05), but not with HT. proMMP-10 levels were also independently and positively associated with circulating levels of TNFα (P < 0.0001), which induced its endothelial expression in vitro, both mRNA and protein. MMP-9, however, was only associated with HT and severe edema (all P < 0.05).
Increased serum proMMP-10 after acute ischemic stroke, associated with TNFα, is a new marker of brain damage and poor outcome.
基质金属蛋白酶（MMPs）在中风期间介导组织损伤，但也介导神经血管重塑，我们已经表明 MMP-10 参与动脉血栓形成。
本研究旨在研究急性缺血性中风患者中 proMMP-10 与临床结果的关系，评估炎症和蛋白水解标志物。
我们前瞻性研究了 76 例在症状发作后 3 小时内接受 tPA 治疗的缺血性中风患者，与 202 例未接受 tPA 治疗的缺血性中风患者和 83 例无症状患者进行比较。中风严重程度采用国立卫生研究院中风量表（NIHSS）评估。出血性转化（HT）和严重脑水肿通过头颅 CT 诊断。90 天的改良 Rankin 量表评分≤2 定义为良好的功能结局。入院时测定 MMP-9、proMMP-10、TIMP-1、肿瘤坏死因子-α（TNFα）、白细胞介素-6 和细胞纤维连接蛋白的血清水平。在体外评估 TNFα 对内皮 proMMP-10 的影响。
缺血性中风患者、未经 t-PA 治疗或接受 t-PA 治疗的患者的血清 proMMP-10 浓度高于年龄匹配的健康受试者（P<0.0001），与更高的梗死体积、严重脑水肿、神经恶化和 3 个月时不良功能结局独立相关（均 P<0.05），但与 HT 无关。proMMP-10 水平也与循环 TNFα 水平独立正相关（P<0.0001），后者在体外诱导其内皮表达，包括 mRNA 和蛋白质。然而，MMP-9 仅与 HT 和严重水肿相关（均 P<0.05）。
急性缺血性中风后血清 proMMP-10 增加，与 TNFα 相关，是脑损伤和不良结局的新标志物。
