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心脑血管疾病中甘露聚糖结合凝集素(MBL)相关丝氨酸蛋白酶(MASPs)和 MBL 相关蛋白的血浆水平。

Plasma levels of mannan-binding lectin (MBL)-associated serine proteases (MASPs) and MBL-associated protein in cardio- and cerebrovascular diseases.

机构信息

University Clinic of Haematology, Haemostasis Research Laboratory, University Hospital and University of Bern, Switzerland.

出版信息

Clin Exp Immunol. 2013 Jul;173(1):112-20. doi: 10.1111/cei.12093.

Abstract

Growing evidence suggests a prominent role of the complement system in the pathogenesis of cardio- and cerebrovascular diseases (CVD). Mannan-binding lectin-associated serine proteases (MASPs) MASP-1 and MASP-2 of the complement lectin pathway contribute to clot formation and may represent an important link between inflammation and thrombosis. MBL-associated protein MAp44 has shown cardioprotective effects in murine models. However, MAp44 has never been measured in patients with CVD and data on MASP levels in CVD are scarce. Our aim was to investigate for the first time plasma levels of MAp44 and MASP-1, -2, -3 concomitantly in patients with CVD. We performed a pilot study in 50 healthy volunteers, in stable coronary artery disease (CAD) patients with one-vessel (n = 51) or three-vessel disease (n = 53) and age-matched controls with normal coronary arteries (n = 53), 49 patients after myocardial infarction (MI) and 66 patients with acute ischaemic stroke. We measured MAp44 and MASP-1 levels by in-house time-resolved immunofluorometric assays. MASP-2 and MASP-3 levels were measured using commercial enzyme-linked immunosorbent assay kits. MASP-1 levels were highest in subacute MI patients and lowest in acute stroke patients. MASP-2 levels were lower in MI and stroke patients compared with controls and CAD patients. MASP-3 and MAp44 levels did not differ between groups. MASP or MAp44 levels were not associated with severity of disease. MASP and MAp44 levels were associated with cardiovascular risk factors including dyslipidaemia, obesity and hypertension. Our results suggest that MASP levels may be altered in vascular diseases. Larger studies are needed to confirm our results and elucidate the underlying mechanisms.

摘要

越来越多的证据表明补体系统在心血管疾病(CVD)的发病机制中起着重要作用。补体凝集素途径中的甘露聚糖结合凝集素相关丝氨酸蛋白酶(MASPs)MASP-1 和 MASP-2 有助于血栓形成,可能是炎症和血栓形成之间的重要联系。MBL 相关蛋白 MAp44 在小鼠模型中显示出心脏保护作用。然而,MAp44 从未在 CVD 患者中测量过,关于 CVD 中 MASP 水平的数据也很少。我们的目的是首次在 CVD 患者中同时检测 MAp44 和 MASP-1、-2、-3 的血浆水平。我们在 50 名健康志愿者、单支病变(n=51)或三支病变(n=53)稳定型冠状动脉疾病(CAD)患者和年龄匹配的正常冠状动脉患者(n=53)中进行了一项试点研究,49 名心肌梗死(MI)后患者和 66 名急性缺血性中风患者。我们使用内部时间分辨免疫荧光测定法测量 MAp44 和 MASP-1 水平。使用商业酶联免疫吸附测定试剂盒测量 MASP-2 和 MASP-3 水平。亚急性 MI 患者的 MASP-1 水平最高,急性中风患者的水平最低。与对照组和 CAD 患者相比,MI 和中风患者的 MASP-2 水平较低。MASP-3 和 MAp44 水平在各组之间没有差异。MASP 或 MAp44 水平与疾病严重程度无关。MASP 和 MAp44 水平与心血管危险因素相关,包括血脂异常、肥胖和高血压。我们的结果表明,MASP 水平可能在血管疾病中发生改变。需要更大的研究来证实我们的结果并阐明潜在的机制。

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