VEGF and angiopoietin-1 stimulate different angiogenic phenotypes that combine to enhance functional neovascularization in adult tissue
VEGF and angiopoietin-1 stimulate different angiogenic phenotypes that combine to enhance functional neovascularization in adult tissue
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DOI：
10.1080/10739680600775940
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发表时间：
2006-09-01
期刊：
影响因子：
2.4
通讯作者：
Bates, David O.
中科院分区：
文献类型：
--
作者：
Benest, Andrew V.;Salmon, Andrew H.;Bates, David O.
目的：治疗性血管生成需要了解生长因子如血管内皮生长因子（VEGF）和血管生成素-1（Ang-1）如何导致生理性新血管形成。本研究确定了腺病毒递送的生长因子组合改变血管表型和functional.Methods的生理机制：腺病毒介导的基因转移到大鼠肠系膜的相邻脂肪垫中，用于表征VEGF和Ang-1诱导血管生成的模型，该模型允许对新生血管表型进行详细检查。Ang-1与VEGF联合导致与单独的任一因子不同的血管表型。微血管灌注在所有组中均显著增强，但VEGF产生短、窄、高度分支和出芽的血管，具有正常的周细胞覆盖。血管紧张素-1诱导更广泛，更长的新生血管，没有增加分支或发芽，但显着更高的周细胞鞘。Ang-1和VEGF的组合产生了显著更高程度的功能灌注的、更大的、分支更少的和更成熟的微血管，这是由于芽到血管形成的效率增加。Ang-1和VEGF也造成了不同的影响，较大的血管相比，较小的血管，一个发现reproduced in vitro. Conclusions：Ang-1和VEGF使用不同的生理机制，以提高相对无血管组织的新血管形成。两种生长因子的施用结合了这些生理机制，以比单独的任一生长因子更大地增强新血管形成。这些结果表明，有效的血运重建治疗可能需要联合生长因子治疗。
Objective: Therapeutic angiogenesis requires an understanding of how growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) result in physiological neovascularization. This study determined the physiological mechanism by which adenoviral delivery of growth factor combinations alter vascular phenotype and functionality.Methods: Adenovirus-mediated gene transfer into the adjacent fat pad of the rat mesentery was used to characterize induction of angiogenesis by VEGF and Ang-1, in a model that permitted a detailed examination of the neovessel phenotype.Results: Ang-1 combined with VEGF resulted in a distinct vascular phenotype from either factor alone. Microvascular perfusion was significantly enhanced in all groups, but VEGF produced short, narrow, highly branched and sprouting vessels, with normal pericyte coverage. Ang-1 induced broader, longer neovessels, with no increase in branching or sprouting, yet a significantly higher pericyte ensheathment. Combination of Ang-1 and VEGF generated a significantly higher degree of functionally perfused, larger, less branched, and more mature microvessels, resulting from increased efficiency of sprout to vessel formation. Ang-1 and VEGF also caused differential effects on larger compared with smaller blood vessels, a finding reproduced in vitro.Conclusions: Ang-1 and VEGF use different physiological mechanisms to enhance neovascularization of relatively avascular tissue. Administration of both growth factors combines these physiological mechanisms to give greater enhancement of neovascularization than either growth factor alone. These results suggest that effective revascularization therapy may require combination growth factor treatment.