How do angiopoietins Tie in with vascular endothelial growth factors?
How do angiopoietins Tie in with vascular endothelial growth factors?
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DOI：
10.1097/moh.0b013e3283386673
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发表时间：
2010-05-01
影响因子：
3.2
通讯作者：
Alitalo, Kari
中科院分区：
文献类型：
--
作者：
Saharinen, Pipsa;Bry, Maija;Alitalo, Kari
综述的目的血管和淋巴管的内皮细胞与人类常见疾病有关。过度的血液和淋巴管生长促进肿瘤进展和转移，而生长不足导致组织缺血和水肿。淋巴管和血管内皮细胞受两种内皮特异性受体酪氨酸激酶系统调节，即分别由VEGF和血管生成素配体激活的血管内皮生长因子（VEGF）受体（VEGFR）和Tie受体。阻断VEGF-VEGFR-2通路已成为肿瘤治疗的第一个抗血管生成策略，在此我们讨论其他通路，特别是血管生成素（Angiopoietin，Ang）-Tie受体通路。最近的发现VEGF激活的VEGFR-2是血管生成信号的主要转导子，但最近的结果表明，淋巴管生成的VEGFR-3也诱导血管生成出芽。VEGF-B是VEGF家族的成员，具有低血管生成活性，已发现其参与心脏能量代谢的调节。最近的报道表明Ang 2参与肿瘤血管生成，并揭示Tie 2在内皮细胞-细胞连接处利用独特的信号传导机制。因此，靶向两个系统可能有利于使抗/促血管生成疗法的功效最大化。
Purpose of reviewThe endothelial cells of the blood and lymphatic vessels are involved in common human diseases. Excess blood and lymphatic vessel growth enhances tumor progression and metastasis, whereas insufficient growth leads to tissue ischemia and lymphedema. Lymphatic and blood vascular endothelial cells are regulated by two endothelial specific receptor tyrosine kinase systems, the vascular endothelial growth factor (VEGF) receptors (VEGFRs) and the Tie receptors, activated by the VEGF and angiopoietin ligands, respectively. Blocking of the VEGF-VEGFR-2 pathway has provided the first antiangiogenic strategy for cancer therapy and here we discuss the other pathways where progress is made for drug development, in particular the angiopoietin (Ang)-Tie receptor pathway.Recent findingsVEGF-activated VEGFR-2 is the major transducer of angiogenic signals, but recent results show that the lymphangiogenic VEGFR-3 induces angiogenic sprouting as well. VEGF-B, a member of the VEGF family with low angiogenic activity, has been found to be involved in the regulation of energy metabolism in the heart. Recent reports have implicated Ang2 in tumor angiogenesis and revealed that Tie2 utilizes a unique signaling mechanism at endothelial cell-cell junctions.SummaryThe VEGF-VEGFR and Ang -Tie systems regulate different aspects of blood and lymphatic vessel growth. Thus, targeting both systems may be beneficial in maximizing the efficacy of anti/pro-angiogenic therapies.