In vivo actions of angiopoietins on quiescent and remodeling blood and lymphatic vessels in mouse airways and skin
In vivo actions of angiopoietins on quiescent and remodeling blood and lymphatic vessels in mouse airways and skin
复制标题
DOI：
10.1161/01.atv.0000256458.82320.be
复制
发表时间：
2007-03-01
影响因子：
8.7
通讯作者：
Koh, Gou Young
中科院分区：
文献类型：
--
作者：
Kim, Kyung Eun;Cho, Chung-Hyun;Koh, Gou Young
目的：我们研究并比较了四种血管生成素(comp-Ang1、Ang2、Ang3和Ang4)对成年小鼠血液和淋巴管重构的影响。我们分析了气管和耳朵皮肤的微血管结构，并将静止的皮肤微血管结构与伤口愈合期间的微血管结构进行了比较。方法和结果-我们能够使用腺病毒递送系统实现每种血管生成素相对长期和持续循环表达的相似水平。治疗2周后，我们观察到气管血液和淋巴管增大，淋巴管丝状细胞形成，其效力顺序如下：Comp-Ang1&Gt；Ang3=Ang4&Gt；Ang2。与Ang2联合治疗可减轻Ang1诱导的气管血液和淋巴管重塑。在正常的耳部皮肤中，所有的血管生成素都能诱导血管扩张，而不能诱导淋巴管重塑。而在耳部皮肤创面愈合缘处，所有血管生成素均强烈诱导淋巴管扩张，形成淋巴球和丝状足，同时促进血管扩张。Ang2和Ang1的联合治疗对这些变化产生了相加效应。结论--这项研究是我们所知的第一个表征所有4种血管生成素在体内的作用的研究之一，可能扩展目前使用血管生成素治疗血管生成和淋巴管生成的概念。
Objective-We investigated and compared the in vivo effects of all four angiopoietins (COMP-Ang1, Ang2, Ang3, and Ang4) on blood and lymphatic vascular remodeling in adult mice. We analyzed the microvasculature of trachea and ear skin, and compared quiescent skin microvasculature with that during wound healing.Methods and Results-We were able to achieve similar levels of relatively long-term and sustained circulating expression of each angiopoietin using an adenoviral delivery system. Two weeks after treatment, we observed tracheal blood and lymphatic vascular enlargement, and lymphatic filopodia formation, with the following order of potency: COMP-Ang1 > Ang3 = Ang4 > Ang2. Co-treatment with Ang2 attenuated Ang1-induced tracheal blood and lymphatic remodeling. In the normal ear skin, all angiopoietins induced blood vessel enlargement, whereas none induced lymphatic vascular remodeling. However, in the healing margin of ear skin wounds, all angiopoietins strongly induced lymphatic vascular enlargement and formation of lymphatic sprouts and filopodia, while they potentiated blood vascular enlargement. Co- treatment of Ang2 with Ang1 produced an additive effect on these changes.Conclusion-This study, one of the first to our knowledge to characterize the in vivo actions of all 4 angiopoietins, may expand the current concepts for use of angiopoietins for therapeutic angiogenesis and lymphangiogenesis.