Dellian M, Witwer B P, Salehi H A, Yuan F, Jain R K
E.L. Steele Laboratory, Department of Radiation Oncology, MassachusettsGeneral Hospital, Boston, USA.
Am J Pathol. 1996 Jul;149(1):59-71.
A prerequisite for the development of novel angiogenic and anti-angiogenic agents is the availability of routine in vivo assays that permit 1) repeated, long-term quantitation of angiogenesis and 2) physiological characterization of angiogenic vessels. We report here the development of such an assay in mice. Using this assay, we tested the hypothesis that the physiological properties of angiogenic vessels governed by the microenvironment and vessel origin rather than the initial angiogenic stimulus. Gels containing basic fibroblast growth factor (bFGF) or vascular endothelial growth (VEGF) were implanted in transparent windows in the dorsal skin or cranium of mice. Vessels could be continuously and non-invasively monitored and easily quantified for more than 5 weeks after gel implantation. Newly formed vessels were first visible on day 4 in the cranial window and day 10 in the dorsal skinfold chamber, respectively. The number of vessels was dependent on the dose of bFGF and VEGF. At 3000 ng/ml, bFGF- and VEGF-induced blood vessels had similar diameters, red blood cell velocities, and microvascular permeability to albumin. However, red blood cell velocities and microvascular permeability to albumin were higher in the cranial window than in the dorsal skinfold chamber. Leukocyte-endothelial interaction was nearly zero in both sites. Thus, newly grown microvessels resembled vessels of granulation and neoplastic tissue in many aspects. Their physiological properties were mainly determined by the microenvironment, whereas the initial angiogenic response was stimulated by growth factors.
开发新型血管生成和抗血管生成药物的一个先决条件是要有常规的体内检测方法，该方法要能实现：1）对血管生成进行重复、长期的定量分析；2）对血管生成血管进行生理学特征描述。我们在此报告了一种在小鼠体内的检测方法的开发情况。利用该检测方法，我们验证了这样一个假设：血管生成血管的生理特性由微环境和血管起源决定，而非初始血管生成刺激因素。将含有碱性成纤维细胞生长因子（bFGF）或血管内皮生长因子（VEGF）的凝胶植入小鼠背部皮肤或颅骨的透明窗口中。凝胶植入后5周多的时间里，可以对血管进行连续、非侵入性监测且易于定量分析。新形成的血管分别在第4天在颅骨窗口中首次可见，在第10天在背部皮褶腔中首次可见。血管数量取决于bFGF和VEGF的剂量。在3000 ng/ml时，bFGF和VEGF诱导的血管具有相似的直径、红细胞速度以及对白蛋白的微血管通透性。然而，颅骨窗口中红细胞速度和对白蛋白的微血管通透性高于背部皮褶腔。两个部位的白细胞与内皮细胞相互作用几乎为零。因此，新生长的微血管在许多方面类似于肉芽组织和肿瘤组织的血管。它们的生理特性主要由微环境决定，而初始血管生成反应则由生长因子刺激产生。
