Abnormal balance in the angiopoietin-Tie2 system in human brain arteriovenous malformations

Abnormal balance in the angiopoietin-Tie2 system in human brain arteriovenous malformations
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DOI:
10.1161/hh1401.094281
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发表时间:
2001-07-20
影响因子:
20.1
通讯作者:
Young, WL
Young, WL
中科院分区:
医学1区
文献类型:
--
作者:
Hashimoto, T;Lam, T;Young, WL

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脑动静脉畸形(BAVM)是先天性血管病变,在年轻人中通常表现为脑出血。临床病程的可变性,特别是自发性出血、复发、生长和消退,表明 BAVM 是具有活跃血管生成和血管重塑的病变。我们通过半定量逆转录酶-聚合酶链反应、原位杂交和蛋白质印迹法检查了 BAVM 和从颞叶切除术获得的医学上难治性癫痫发作的对照大脑中血管生成素 1 (Ang1) 和 Ang2 的 mRNA 和蛋白表达。尽管 BAVM 和对照中的 Ang1 mRNA 水平相似,但 BAVM 中的 Ang1 蛋白水平比对照低 30%。 BAVM 中的 Ang2 mRNA 水平比对照组高 40%,Ang2 蛋白水平高 8 倍。原位杂交显示 Ang2 mRNA 定位于 BAVM 的血管周围区域。 Ang-Tie2 系统中的这种异常平衡可能部分解释了 BAVM 中异常的血管表型。
Brain arteriovenous malformations (BAVMs) are congenital vascular lesions that often present as cerebral hemorrhage in young adults. The variable nature of the clinical course, especially with respect to spontaneous hemorrhage, recurrence, growth, and regression, suggests that BAVMs are lesions with active angiogenesis and vascular remodeling. We examined mRNA and protein expression of angiopoietin 1 (Ang1) and Ang2 by semiquantitative reverse transcriptase-polymerase chain reaction, in situ hybridization, and Western blot in BAVMs and control brains obtained from temporal lobectomy for medically intractable seizures. Although Ang1 mRNA levels were similar in BAVMs and controls, Ang1 protein levels were 30% lower in BAVMs than in controls. Ang2 mRNA levels were 40% higher and Ang2 protein levels were 8-fold higher in BAVMs than in controls. In situ hybridization showed that the Ang2 mRNA was localized to the perivascular area in BAVMs. This abnormal balance in the Ang-Tie2 system may, in part, explain the aberrant vascular phenotype in BAVMs.