Department of Surgery, James Paget Hospital, Lowestoft Road, Gorleston, Norfolk, England NR31 6LA, United Kingdom.
Cytokine Growth Factor Rev. 2013 Dec;24(6):579-92. doi: 10.1016/j.cytogfr.2013.05.009. Epub 2013 Jul 6.
Angiopoietin-1 and -2 are endogenous ligands for the vascular endothelial receptor tyrosine kinase Tie2. Signalling by angiopoietin-1 promotes vascular endothelial cell survival and the sprouting and reorganisation of blood vessels, as well as inhibiting activation of the vascular endothelial barrier to reduce leakage and leucocyte migration into tissues. Angiopoietin-2 generally has an opposing action, and is released naturally at times of vascular growth and inflammation. There is a significant body of emerging evidence that promoting the actions of angiopoietin-1 through Tie2 is of benefit in pathologies of vascular activation, such as sepsis, stroke, diabetic retinopathy and asthma. Similarly, methods to inhibit the actions of angiopoietin-2 are emerging and have been demonstrated to be of preclinical and clinical benefit in reducing tumour angiogenesis. Here the author reviews the evidence for potential benefits of modulation of the interaction of angiopoietins with Tie2, and the potential applications. Additionally, methods for delivery of the complex protein angiopoietin-1 are discussed, as well as potentially deleterious consequences of administering angiopoietin-1.
血管生成素-1 和 -2 是血管内皮受体酪氨酸激酶 Tie2 的内源性配体。血管生成素-1 的信号转导促进血管内皮细胞存活以及血管的发芽和重组，同时抑制血管内皮屏障的激活以减少渗漏和白细胞向组织的迁移。血管生成素-2 通常具有相反的作用，并在血管生长和炎症时自然释放。有大量新出现的证据表明，通过 Tie2 促进血管生成素-1 的作用有益于血管激活的病理学，例如败血症、中风、糖尿病视网膜病变和哮喘。同样，抑制血管生成素-2 作用的方法也在不断涌现，并已被证明在减少肿瘤血管生成方面具有临床前和临床益处。作者在这里回顾了调节血管生成素与 Tie2 相互作用的潜在益处的证据，以及潜在的应用。此外，还讨论了复杂蛋白血管生成素-1 的传递方法，以及给予血管生成素-1 可能带来的有害后果。
