VEGF and Angiopoietins Promote Inflammatory Cell Recruitment and Mature Blood Vessel Formation in Murine Sponge/Matrigel Model
VEGF and Angiopoietins Promote Inflammatory Cell Recruitment and Mature Blood Vessel Formation in Murine Sponge/Matrigel Model
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DOI：
10.1002/jcb.24941
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发表时间：
2015-01-01
影响因子：
4
通讯作者：
Sirois, Martin G.
中科院分区：
文献类型：
--
作者：
Sinnathamby, Tharsika;Yun, JinTae;Sirois, Martin G.
诱导病理性血管生成的一个关键特征是炎症先于并伴随新血管的形成，如通过增加的血管渗透性和炎症细胞的募集所证明的。以前，我们和其他小组已经表明，选定的生长因子，即血管内皮生长因子（VEGF）和血管生成素（Ang 1和Ang 2）不仅促进血管生成，但也可以诱导炎症反应。在此，给定促炎环境，我们讨论了VEGF和血管生成素促进成熟新血管形成的个体能力，并鉴定随时间推移伴随血管生成过程的不同类型的炎性细胞。将浸泡在与PBS、VEGF、Ang 1或Ang 2（200 ng/200 μ l）混合的生长因子耗尽的Matrigel中的灭菌聚乙烯醇（PVA）海绵皮下插入麻醉小鼠。在术后第4、7、14或21天取出海绵进行组织学、免疫组织学（IHC）和流式细胞术分析。与PBS处理的海绵相比，三种生长因子促进了炎症细胞的募集，主要是中性粒细胞和巨噬细胞，以及在较小程度上促进了T细胞和B细胞的募集。此外，它们在内皮细胞（EC）的募集以及新生血管的形成和成熟（EC周围平滑肌细胞的鞘化）方面更有效、更迅速。因此，与VEGF、Ang 1或Ang 2组合的不同炎性细胞之间的自分泌/旁分泌相互作用为血管的形成和成熟提供了合适的微环境。J.细胞。116：45-57，2015. (c)2014 Wiley Periodicals，Inc.
A key feature in the induction of pathological angiogenesis is that inflammation precedes and accompanies the formation of neovessels as evidenced by increased vascular permeability and the recruitment of inflammatory cells. Previously, we and other groups have shown that selected growth factors, namely vascular endothelial growth factor (VEGF) and angiopoietins (Ang1 and Ang2) do not only promote angiogenesis, but can also induce inflammatory response. Herein, given a pro-inflammatory environment, we addressed the individual capacity of VEGF and angiopoietins to promote the formation of mature neovessels and to identify the different types of inflammatory cells accompanying the angiogenic process over time. Sterilized polyvinyl alcohol (PVA) sponges soaked in growth factor-depleted Matrigel mixed with PBS, VEGF, Ang1, or Ang2 (200ng/200 mu l) were subcutaneously inserted into anesthetized mice. Sponges were removed at day 4, 7, 14, or 21 post-procedure for histological, immunohistological (IHC), and flow cytometry analyses. As compared to PBS-treated sponges, the three growth factors promoted the recruitment of inflammatory cells, mainly neutrophils and macrophages, and to a lesser extent, T- and B-cells. In addition, they were more potent and more rapid in the recruitment of endothelial cells (ECs) and in the formation and maturation (ensheating of smooth muscle cells around ECs) of neovessels. Thus, the autocrine/paracrine interaction among the different inflammatory cells in combination with VEGF, Ang1, or Ang2 provides a suitable microenvironment for the formation and maturation of blood vessels. J. Cell. Biochem. 116: 45-57, 2015. (c) 2014 Wiley Periodicals, Inc.