Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
J Neurol. 2013 Oct;260(10):2642-9. doi: 10.1007/s00415-013-7040-x. Epub 2013 Jul 23.
Alpha2-macroglobulin is a protease inhibitor that enhances procoagulant properties via the neutralization of plasmin, plasminogen activators and metalloproteinases. Additionally, alpha2-macroglobulin is thought to be involved in inflammatory reactions as a carrier protein for interleukin-6 (IL-6). The objective of this study was to evaluate the usefulness of alpha2-macroglobulin as a biomarker for cerebrovascular diseases. Patients with acute ischemic stroke (n = 159; 93 male and 66 female, 71.6 ± 10.3 years) and patients with no previous history of stroke (n = 77; 38 male and 39 female, 70.7 ± 9.5 years) were consecutively enrolled in this study. White matter lesions were assessed via the fluid-attenuated inversion recovery image of magnetic resonance images using the Fazekas classification. The serum alpha2-macroglobulin levels were measured by nephelometry. The serum alpha2-macroglobulin levels at admission in patients with acute ischemic stroke were higher than those in the control patients (230.2 ± 73.7 vs. 205.0 ± 55.8 mg/dl, p = 0.009). The serum alpha2-macroglobulin levels were positively correlated with age and the severity of the white matter lesions (R (2) = 0.048, p < 0.001 and R (2) = 0.058, p < 0.001, respectively), although there was no significant association between serum alpha2-macroglobulin levels and IL-6 levels. In addition, multivariate analysis showed that increased serum alpha2-macroglobulin levels were independently associated with the severity of white matter lesions [standardized partial regression coefficient (β) 0.102, p = 0.026]. Increased serum alpha2-macroglobulin levels might be involved in the pathophysiology of acute ischemic stroke. Furthermore, serum alpha2-macroglobulin levels, which were associated with high-grade white matter lesions, may reflect the chronic pathophysiological condition of cerebral small vessel disease.
α2-巨球蛋白是一种蛋白酶抑制剂，通过中和纤溶酶、纤溶酶原激活物和金属蛋白酶来增强促凝特性。此外，α2-巨球蛋白被认为作为白细胞介素-6（IL-6）的载体蛋白参与炎症反应。本研究旨在评估α2-巨球蛋白作为脑血管疾病生物标志物的有用性。连续纳入 159 例急性缺血性脑卒中患者（93 例男性，66 例女性；71.6±10.3 岁）和 77 例无脑卒中病史的患者（38 例男性，39 例女性；70.7±9.5 岁）。采用磁共振成像液体衰减反转恢复图像，采用 Fazekas 分级评估脑白质病变。通过散射比浊法测量血清α2-巨球蛋白水平。急性缺血性脑卒中患者入院时血清α2-巨球蛋白水平高于对照组（230.2±73.7 比 205.0±55.8 mg/dl，p=0.009）。血清α2-巨球蛋白水平与年龄和脑白质病变严重程度呈正相关（R²=0.048，p<0.001 和 R²=0.058，p<0.001），但血清α2-巨球蛋白水平与 IL-6 水平无显著相关性。此外，多元分析显示，血清α2-巨球蛋白水平升高与脑白质病变严重程度独立相关[标准化偏回归系数（β）0.102，p=0.026]。升高的血清α2-巨球蛋白水平可能参与急性缺血性脑卒中的病理生理过程。此外，与高级别脑白质病变相关的血清α2-巨球蛋白水平可能反映了脑小血管疾病的慢性病理生理状况。
