Growth factors reverse the impaired sprouting of microvessels from aged mice
Growth factors reverse the impaired sprouting of microvessels from aged mice
复制标题
DOI：
10.1006/mvre.1998.2078
复制
发表时间：
1998-05-01
影响因子：
3.1
通讯作者：
Reed, MJ
中科院分区：
文献类型：
--
作者：
Arthur, WT;Vernon, RB;Reed, MJ
衰老伴随着血管生成的受损和几种血管生成生长因子的表达不足。为了验证这些因素的替代将促进老年动物血管生成的假设，我们在三维胶原凝胶中培养了老年和年轻小鼠附睾脂垫微血管2周，并检测了它们对胎牛血清(FBS)、内皮细胞生长补充剂(ECGs)和特异性生长因子转化生长因子-β1(TGF-β1)、血管内皮生长因子(VEGF)、胰岛素样生长因子-1(IGF-1)和碱性成纤维细胞生长因子(BFGF)的反应(分支点形成)。在含有1%胎牛血清的培养液中，老年微血管的萌发明显少于年轻微血管的萌发。在微量培养液中加入高水平的胎牛血清和鸡蛋，比起幼龄鼠更能促进老龄鼠微血管的萌发，因此两个年龄组之间的差异不再显著。在微量培养液中添加转化生长因子-β1、碱性成纤维细胞生长因子、胰岛素样生长因子-1或血管内皮生长因子(按刺激程度从高到低的顺序排列)，也能显著增加老年微血管的分支点的形成。在有血管内皮生长因子存在的情况下产生的芽具有特别高比例的内皮细胞。丝裂霉素C不能减少转化生长因子-β1、血管内皮生长因子或胰岛素样生长因子-1诱导的萌发程度，这一结果表明，血管生成的早期阶段，包括分支点的形成，不需要细胞分裂。根据我们在体外的发现，我们认为体内血管生成中与年龄相关的缺陷可能部分是由于细胞外环境中血管生成生长因子的减少。(C)1998年学术出版社。
Aging is accompanied by impaired angiogenesis and deficient expression of several angiogenic growth factors. To test the hypothesis that replacement of these factors would improve angiogenesis in aged animals, we cultured microvessels derived from the epididymal fat pad of aged and young mice ("aged" and "young" microvessels) in three-dimensional collagen gels for 2 weeks and measured their sprouting (formation of branch points) in response to fetal bovine serum (FBS), endothelial cell growth supplement (ECGS), and the specific growth factors transforming growth factor-beta 1 (TGF-beta 1), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (bFGF). In the presence of culture medium with 1% FBS (Minimal medium), sprouting of aged microvessels was significantly less than sprouting of young microvessels. The addition of high levels of FBS and EGGS to Minimal medium enhanced the sprouting of microvessels from aged mice to a greater degree than that of young mice, such that the difference between the two age groups was no longer significant. Formation of branch points by aged microvessels was also significantly increased by Minimal medium supplemented with TGF-beta 1, bFGF, IGF-1, or VEGF (listed in order of highest to lowest stimulation). Sprouts generated in the presence of VEGF possessed a particularly high percentage of endothelial cells. Mitomycin C did not diminish the degree of sprouting induced by TGF-beta 1, VEGF, or IGF-1, a result indicating that early stages of angiogenesis, including formation of branch points, do not require cell division. From our findings in vitro, we propose that age-related deficiencies in angiogenesis in vivo are likely to be due, in part, to a decrease in angiogenic growth factors in the extracellular milieu. (C) 1998 Academic Press.