ANGIOGENESIS - INITIATION AND CONTROL

ANGIOGENESIS - INITIATION AND CONTROL
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DOI:
10.1111/j.1749-6632.1982.tb25720.x
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发表时间:
1982-01-01
影响因子:
5.2
通讯作者:
FOLKMAN, J
FOLKMAN, J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
FOLKMAN, J

文献摘要

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从使用新方法(如兔角膜)的体内实验中,现在变得清楚的是,毛细血管的生长涉及一系列有序的事件,包括母微静脉基底膜的溶解、毛细血管内皮细胞向血管生成刺激物的定向迁移、管腔形成、分支的发育以及一个管的尖端与另一个管的尖端吻合以形成环。同样清楚的是,扩散性血管生成刺激不仅可以从大多数实体瘤中释放,而且可以从至少三种非肿瘤细胞中释放。这些包括活化的巨噬细胞、致敏淋巴细胞和脂肪细胞。其他正常组织也可以刺激血管生成,但是引起血管生成刺激的细胞类型是未知的,并且血管生成刺激的时间是短暂的。随着最近克隆毛细血管内皮细胞并将其长期培养的能力,有可能进一步阐明毛细血管生长的机制。体外研究表明,肥大细胞似乎是毛细血管内皮细胞的辅助细胞,在某种程度上加快了它们定向迁移的速度。在这篇文章中,肝素似乎是主要的肥大细胞因子负责这种影响毛细血管内皮细胞。一种理论上的可能性是,肥大细胞可能通过缓慢释放肝素来准备基质,这样毛细血管芽就可以更容易地穿过基质向它们的血管生成目标移动。虽然对血管生成作为一种现象的研究仍处于早期阶段,但通过使用体外和体内技术的组合,已经有可能更彻底地了解毛细血管生长的启动和控制。
From in vivo experiments using new methods such as the rabbit cornea, it is now becoming clear that the growth of a capillary involves an ordered sequence of events that includes lysis of the basement membrane of a parent venule, directional migration of capillary endothelial cells toward the angiogenic stimulus, lumen formation, development of branches, and anastomosis of the tip of one tube with another to form a loop. It is also clear that diffusible angiogenic stimuli can be released not only from most solid tumors, but also from at least three non-neoplastic cells. These include activated macrophages, sensitized lymphocytes, and adipocytes. Other normal tissues can also stimulate angiogenesis, but the type of cell giving rise to the angiogenic stimulus is unknown, and the period of angiogenic stimulation is brief. With the recent ability to clone capillary endothelial cells and to carry them in long-term culture, it has been possible to further delineate the mechanism of capillary growth. In vitro studies have shown that the mast cell seems to behave as a helper cell for capillary endothelial cells, in some way speeding up their rate of directional migration. At this writing, heparin appears to be the principal mast cell factor responsible for this effect on capillary endothelial cells. One theoretical possibility is that mast cells may prepare the matrix, perhaps by slow release of heparin, so that capillary sprouts can more easily move through it toward their angiogenic target. While the study of angiogenesis as a phenomenon is still in an early phase, it has become possible, by using a combination of in vitro and in vivo techniques, to more thoroughly understand the initiation and control of capillary growth.