Long-term and sustained COMP-Ang1 induces long-lasting vascular enlargement and enhanced blood flow
Long-term and sustained COMP-Ang1 induces long-lasting vascular enlargement and enhanced blood flow
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DOI：
10.1161/01.res.0000174093.64855.a6
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发表时间：
2005-07-08
影响因子：
20.1
通讯作者：
Koh, GY
中科院分区：
文献类型：
--
作者：
Cho, CH;Kim, KE;Koh, GY
血管扩张是血管生成素-1（Ang 1）诱导的成人血管变化的特征。然而，尚不清楚具有Ang 1介导的血管扩张的组织是否具有更多的血流量或扩张是否可逆。我们最近创造了一种可溶的，稳定的和有效的Ang 1变体，COMP-Ang 1。在本研究中，我们研究了不同剂量和持续时间的COMP-Ang 1对成年小鼠气管微血管扩张和血流的影响，并探讨了持久的血管扩张的可能机制。我们发现，腺病毒载体给予COMP-Ang 1可诱导持久的血管扩张和增加气管血流量。相反，短期给予COMP-Ang 1重组蛋白诱导短暂的血管扩张，并在一个月内自发逆转。在这两种情况下，血管扩张导致内皮细胞增殖。COMP-Ang 1诱导的血管重构主要通过Tie 2激活介导。Tie 2的持续过表达可能参与了血管病变的维持。总之，我们的研究结果表明，COMP-Ang 1的持续治疗可以产生持久的血管扩张和血流量增加。
Vascular enlargement is a characteristic feature of angiopoietin-1 (Ang1)-induced changes in adult blood vessels. However, it is unknown whether tissues having Ang1-mediated vascular enlargement have more blood flow or whether the enlargement is reversible. We have recently created a soluble, stable and potent Ang1 variant, COMP-Ang1. In the present study, we investigated the effects of varied dose and duration of COMP-Ang1 on vascular enlargement and blood flow in the tracheal microvasculature of adult mice and explored a possible mechanism of long-lasting vascular enlargement. We found that COMP-Ang1 administered by adenoviral vector induced long-lasting vascular enlargement and increased tracheal blood flow. In contrast, short-term administration of COMP-Ang1 recombinant protein induced transient vascular enlargement that spontaneously reversed within a month. In both cases, the vascular enlargement resulted from endothelial proliferation. The COMP-Ang1-induced vascular remodeling is mediated mainly through Tie2 activation. Sustained overexpression of Tie2 could participate in the maintenance of vascular changes. Together, our findings indicate that sustained treatment with COMP-Ang1 can produce long-lasting vascular enlargement and increased blood flow.