Ang-Tie轴在血管和淋巴系统相关疾病中作用的研究进展

Advances of Angiopoietin-Tie axis in vascular and lymphatic system-related diseases

摘要:

形成血管和淋巴管内层的内皮细胞是脉管系统的重要组成部分，并参与血管和淋巴系统疾病的发病机制。内皮细胞上的血管生成素 (Angiopoietin，Ang)-具有免疫球蛋白和表皮生长因子同源性结构域的酪氨酸蛋白激酶 (Tyrosine kinase receptors with immunoglobulin and EGF homology domains，Tie) 轴是除了血管内皮生长因子受体途径外胚胎心血管和淋巴发育所必需的第二种内皮细胞特异性配体-受体信号传导系统。Ang-Tie轴参与调节产后血管生成与重塑、血管通透性和炎症，以维持血管平衡，因此，该系统在许多血管和淋巴系统疾病中发挥重要的作用。针对近年来Ang-Tie轴在血管和淋巴系统相关疾病中作用的研究进展，文中系统论述了Ang-Tie轴在炎症诱导的血管通透性、血管重塑、眼部新生脉管、剪切应力反应、动脉粥样硬化和肿瘤血管生成和转移中的作用，并总结了涉及Ang-Tie轴的相关治疗性抗体、重组蛋白和小分子药物。

Abstract:

Endothelial cells that form the inner layers of both blood and lymphatic vessels are important components of the vascular system and are involved in the pathogenesis of vascular and lymphatic diseases. Angiopoietin (Ang)-Tie axis in endothelial cells is the second endothelium-specific ligand-receptor signaling system necessary for embryonic cardiovascular and lymphatic development in addition to the vascular endothelial growth factor receptor pathway. The Ang-Tie axis also maintains vascular homeostasis by regulating postnatal angiogenesis, vessel remodeling, vascular permeability, and inflammation. Therefore, the dysfunction of this system leads to many vascular and lymphatic diseases. In light of the recent advances on the role of the Ang-Tie axis in vascular and lymphatic system-related diseases, this review summarizes the functions of the Ang-Tie axis in inflammation-induced vascular permeability, vascular remodeling, ocular angiogenesis, shear stress response, atherosclerosis, tumor angiogenesis, and metastasis. Moreover, this review summarizes the relevant therapeutic antibodies, recombinant proteins, and small molecular drugs associated with the Ang-Tie axis.