Benest Andrew V, Harper Steven J, Herttuala Seppo Yla, Alitalo Kari, Bates David O
Microvascular Research Laboratories, Department of Physiology, University of Bristol, BS2 8EJ Bristol, UK.
Cardiovasc Res. 2008 May 1;78(2):315-23. doi: 10.1093/cvr/cvm094. Epub 2007 Dec 7.
Vascular endothelial growth factor-C (VEGF-C) has been shown to stimulate both angiogenesis and lymphangiogenesis in some but not all models where VEGF-C is over-expressed. Our aim was to investigate the interaction between lymphangiogenesis and angiogenesis in adult tissues regulated by VEGF-C and identify evidence of polarized growth of lymphatics driven by specialized cells at the tip of the growing sprout.
We used an adult model of lymphangiogenesis in the rat mesentery. The angiogenic effect of VEGF-C was markedly attenuated in the presence of a growing lymphatic network. Furthermore, we show that this growth of lymphatic vessels can occur both by recruitment of isolated lymphatic islands to a connected network and by filopodial sprouting. The latter is independent of polarized tip cell differentiation that can be generated all along lymphatic capillaries, independently of the proliferation status of the lymphatic endothelial cells.
These results both demonstrate a dependence of VEGF-C-mediated angiogenesis on lymphatic vascular networks and indicate that the mechanism of VEGF-C-mediated lymphangiogenesis is different from that of classical angiogenic mechanisms.
血管内皮生长因子-C（VEGF-C）在一些（但并非所有）VEGF-C过表达的模型中已显示出既能刺激血管生成又能刺激淋巴管生成。我们的目的是研究在VEGF-C调节的成年组织中淋巴管生成与血管生成之间的相互作用，并确定由生长芽尖的特化细胞驱动的淋巴管极化生长的证据。
我们使用大鼠肠系膜淋巴管生成的成年模型。在存在不断生长的淋巴管网络的情况下，VEGF-C的血管生成作用明显减弱。此外，我们表明，淋巴管的这种生长既可以通过将孤立的淋巴岛募集到相连的网络中发生，也可以通过丝状伪足芽生发生。后者独立于极化的尖端细胞分化，这种分化可以在淋巴管毛细血管全程产生，与淋巴管内皮细胞的增殖状态无关。
这些结果既证明了VEGF-C介导的血管生成对淋巴管网络的依赖性，又表明VEGF-C介导的淋巴管生成机制与经典血管生成机制不同。
