Department of Neurosurgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou Zhejiang Province, China.
Biomed Res Int. 2020 Aug 4;2020:8209313. doi: 10.1155/2020/8209313. eCollection 2020.
Moyamoya disease (MMD) is a progressive occlusive cerebrovascular disease that is characterized by abnormal angiogenesis at the base of the brain. This pathological abnormal angiogenesis is susceptible to disturbances, including spontaneous hemorrhage and vasogenic edema. However, the underlying mechanisms of pathological angiogenesis and occurrence of hemorrhage are unclear. Angiopoietins play a fundamental role in the pathophysiology of central nervous system disorders in angiogenesis. This study was aimed at examining whether angiopoietins are associated with formation of abnormal collateral vessels and the occurrence of hemorrhage in adult-onset moyamoya disease (HMMD).
A total of 27 consecutive adult patients with HMMD were enrolled from June 2011 to May 2017. Serum levels of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) were examined by enzyme-linked immunosorbent assay. Patients with HMMD were compared with those with spontaneous hemorrhage (controls) and nonhemorrhagic-onset MMD (NHMMD).
Serum Ang-2 levels were significantly higher in patients with adult HMMD than in those with spontaneous hemorrhage and NHMMD. The ROC curve identified that a baseline serum Ang-2 level > 1230 ng/ml may be associated with adult HMMD with 88.39% sensitivity and 70.37% specificity (area under the curve (AUC), 0.89; 95% CI, 0.808-0.973; < 0.001). Moreover, serum Ang-2 levels were significantly elevated in stages II, III, and IV. In subgroup analysis of a high and low degree of moyamoya vessels, serum Ang-2 levels were significantly higher in the high moyamoya vessel group than in the low moyamoya vessel group. Serum Ang-2 levels were also significantly higher in the low moyamoya vessel group compared with the control group. Serum Ang-1 levels were not significantly different among the groups.
Increased serum Ang-2 levels may contribute to pathological abnormal angiogenesis and/or to the instability of vascular structure and function, thus causing brain hemorrhage in adult HMMD.
烟雾病（MMD）是一种进展性的脑血管闭塞性疾病，其特征是脑底异常血管生成。这种病理性的异常血管生成容易受到干扰，包括自发性出血和血管源性水肿。然而，病理性血管生成和出血的发生的潜在机制尚不清楚。血管生成素在血管生成的中枢神经系统疾病的病理生理学中起着根本作用。本研究旨在探讨血管生成素是否与成人发病的烟雾病（HMMD）异常侧支血管形成和出血有关。
本研究共纳入 2011 年 6 月至 2017 年 5 月期间 27 例连续的成人 HMMD 患者。通过酶联免疫吸附试验检测血管生成素-1（Ang-1）和血管生成素-2（Ang-2）的血清水平。将 HMMD 患者与自发性出血（对照组）和非出血性 MMH（NHMMD）患者进行比较。
成人 HMMD 患者的血清 Ang-2 水平明显高于自发性出血和 NHMMD 患者。ROC 曲线确定，基线血清 Ang-2 水平>1230ng/ml 可能与成人 HMMD 相关，其敏感性为 88.39%，特异性为 70.37%（曲线下面积（AUC）为 0.89；95%可信区间（CI）为 0.808-0.973；<0.001）。此外，在 II、III 和 IV 期，血清 Ang-2 水平显著升高。在 moyamoya 血管高、低程度的亚组分析中，高 moyamoya 血管组的血清 Ang-2 水平明显高于低 moyamoya 血管组。与对照组相比，低 moyamoya 血管组的血清 Ang-2 水平也明显升高。各组间血清 Ang-1 水平无显著差异。
血清 Ang-2 水平升高可能导致病理性异常血管生成和/或血管结构和功能不稳定，从而导致成人 HMMD 发生脑出血。
