Lymphology Center of Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, People's Republic of China.
Lymphology. 2010 Jun;43(2):59-72.
The angiopoietin/Tie system plays a key role in remodeling and maturation of blood vessels as well as lymphatic vessels. The angiopoietin family includes four ligands (Ang-1, Ang-2 and Ang-3/4) and two corresponding tyrosine kinase receptors (Tie1 and Tie2). The best characterized angiopoietins are Ang-1 and Ang-2. Ang-1 acts as an obligate agonist of the Tie2 receptor. Binding of Ang-1 to Tie2 induces its autophosphorylation and promotes vascular stability and integrity. Ang-1 induces lymphatic vessel enlargement, sprouting and proliferation in a VEGFR-3-dependent manner. In contrast, whether Ang-2 is agonistic or antagonistic is dependent on dose and context. Ang-2 modulates angiogenesis in a cooperative manner with another important angiogenic factor, vascular endothelial growth factor A. In the presence of VEGF-A, Ang-2 promotes vascular sprouting. When in the absence of VEGF-A, Ang-2 induces vascular regression. However, genetic studies have revealed that Ang-2-deficient mice exhibit more severe defects in the lymphatic vasculature than in blood vessels. Ang-2 seems to be involved in the remodeling and stabilization of lymphatic vessels. Although the Ang/Tie system is essential for blood and lymphatic vessel remodeling and maturation, defining its precise role in blood and lymphatic development has been a major challenge. This review provides an update on our current understanding of the angiopoietin/Tie system in lymphangiogenesis.
血管生成素/Tie 系统在血管和淋巴管的重塑和成熟中起着关键作用。血管生成素家族包括四个配体（Ang-1、Ang-2 和 Ang-3/4）和两个相应的酪氨酸激酶受体（Tie1 和 Tie2）。研究最为充分的血管生成素是 Ang-1 和 Ang-2。Ang-1 作为 Tie2 受体的必需激动剂。Ang-1 与 Tie2 的结合诱导其自身磷酸化，并促进血管的稳定性和完整性。Ang-1 以 VEGFR-3 依赖性方式诱导淋巴管扩大、出芽和增殖。相比之下，Ang-2 是激动剂还是拮抗剂取决于剂量和环境。Ang-2 与另一种重要的血管生成因子血管内皮生长因子 A 以协同方式调节血管生成。在 VEGF-A 存在的情况下，Ang-2 促进血管出芽。当缺乏 VEGF-A 时，Ang-2 诱导血管退化。然而，遗传研究表明，Ang-2 缺陷小鼠的淋巴管血管缺陷比血管更严重。Ang-2 似乎参与了淋巴管的重塑和稳定。尽管 Ang/Tie 系统对于血管和淋巴管的重塑和成熟至关重要，但确定其在血液和淋巴管发育中的精确作用一直是一个主要挑战。本综述提供了对淋巴管生成中血管生成素/Tie 系统的最新认识。
