Angiopoietin-4  (血管生成素 4)

血管生成素 (Angiopoietins) 是一类血管生长因子，是酪氨酸激酶受体 Tie-2 的配体。血管生成素主要作用于血管系统，控制血管的发育和稳定。四种不同的血管生成素已被报道：Ang-1, Ang-2, Ang-3和Ang-4。从结构上看，血管生成素包含一个 N 端超聚簇结构域 (SCD)、一个负责配体均聚化的中央卷曲螺旋结构域 (CCD)、一个linker 区和一个与 Tie-2 受体结合所需的 C 端纤维蛋白原相关结构域 (FReD)。血管生成素结合 Tie-2 的第二个免疫球蛋白基序，从而在 Tie-1/Tie-2 异质二聚体中激活 Tie-2和间接激活 Tie-1。 血管生成素 (ANG1-ANG4) 和 Tie-1/2 形成一个内皮信号通路，这是胚胎心血管和淋巴发育所必需的。在成人中，该系统调节血管稳态，并控制血管通透性、炎症和血管生成反应。Ang-1 和 Ang-2 是研究最全面的血管生成素。Ang-1 在血管成熟过程中起重要作用，介导内皮细胞的迁移、粘附和存活。Ang-2破坏内皮细胞和血管周围细胞之间的连接，促进细胞死亡和血管萎缩。

Angiopoietins are a family of vascular growth factors that are ligands for the tyrosine kinase receptor Tie-2. Angiopoietins acts primarily on the vasculature to control blood vessel development and stability. Four distinct angiopoietins have been described: Ang-1, Ang-2, Ang-3 and Ang-4. Structurally, the angiopoietins contain an N-terminal super clustering domain (SCD), a central coiled-coil domain (CCD) responsible for ligand homo-oligomerization, a linker region, and a C-terminal fibrinogen-related domain (FReD) required for binding to the Tie-2 receptor. Angiopoietins bind the second immunoglubulin motif of Tie-2 whereby they activate Tie-2 and, indirectly, Tie-1 in Tie-1/Tie-2 heterodimers. Angiopoietins (ANG1-ANG4) and the Tie-1/2 form an endothelial signalling pathway that is necessary for embryonic cardiovascular and lymphatic development. In adults, this system regulates vascular homeostasis, and controls vessel permeability, inflammation and angiogenic responses. Ang-1 and Ang-2 are the most exhaustively studied angiopoietins. Ang-1 is a critical player in vessel maturation and it mediates migration, adhesion and survival of endothelial cells. Ang-2 disrupts the connections between the endothelium and perivascular cells and promotes cell death and vascular regression.