Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Blood. 2011 Jan 20;117(3):1081-90. doi: 10.1182/blood-2010-02-267427. Epub 2010 Aug 12.
Angio- and lymphangiogenesis are inherently related processes. However, how blood and lymphatic vessels regulate each other is unknown. This work introduces a novel mechanism explaining the temporal and spatial relation of blood and lymphatic vessels. Vascular endothelial growth factor-A (VEGF-A) surprisingly reduced VEGF-C in the supernatant of blood vessel endothelial cells, suggesting growth factor (GF) clearance by the growing endothelium. The orientation of lymphatic sprouting toward angiogenic vessels and away from exogenous GFs was VEGF-C dependent. In vivo molecular imaging revealed higher VEGF receptor (R)-2 in angiogenic tips compared with normal vessels. Consistently, lymphatic growth was impeded in the angiogenic front. VEGF-C/R-2 complex in the cytoplasm of VEGF-A-treated endothelium indicated that receptor-mediated internalization causes GF clearance from the extracellular matrix. GF clearance by receptor-mediated internalization is a new paradigm explaining various characteristics of lymphatics.
血管生成和淋巴管生成是内在相关的过程。然而，血液和淋巴管如何相互调节尚不清楚。这项工作介绍了一种新的机制，解释了血液和淋巴管的时空关系。血管内皮生长因子 A（VEGF-A）出人意料地减少了血管内皮细胞上清液中的 VEGF-C，表明生长因子（GF）被不断生长的内皮清除。淋巴管向血管生成血管定向生长，远离外源性 GFs，这依赖于 VEGF-C。体内分子成像显示，与正常血管相比，血管生成尖端的血管内皮生长因子受体（R）-2 更高。一致地，淋巴管在血管生成前沿受到阻碍。血管内皮生长因子 A 处理的内皮细胞质中的 VEGF-C/R-2 复合物表明，受体介导的内吞作用导致 GF 从细胞外基质中清除。受体介导的内吞作用清除 GF 是一个新的范例，解释了淋巴管的各种特征。
