Inhibitors of basement membrane collagen synthesis prevent endothelial cell alignment in matrigel in vitro and angiogenesis in vivo.
Inhibitors of basement membrane collagen synthesis prevent endothelial cell alignment in matrigel in vitro and angiogenesis in vivo.
复制标题
基底膜胶原蛋白合成抑制剂可防止体外基质胶中的内皮细胞排列和体内血管生成。
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
Maragoudakis Me
中科院分区：
文献类型：
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作者：
G. Haralabopoulos;D. Grant;H. Kleinman;Lelkes Pi;Papaioannou Sp;Maragoudakis Me
背景
基底膜的形成是新血管发育的最后一步。基质胶是一种富含层粘连蛋白的重组基底膜基质，可诱导内皮细胞分化为毛细血管样结构。
实验设计
研究了基底膜胶原合成抑制剂三环癸烷-9-基黄原酸酯（D 609）和溴化8，9-二羟基-7-甲基-苯并[B]喹嗪鎓（GPA 1734）对体外基质胶上内皮细胞管形成和体内C57黑小鼠血管生成测定的影响。
结果
D 609和GPA 1734在体外引起管形成的剂量依赖性减少，其中D 609在50微克/ml和GPA 1734在15微克/ml时完全抑制。两种药物对毛细血管形成的抑制作用是可逆的。管的形成与胶原蛋白的合成密切相关。对在塑料上培养的内皮细胞的平行研究表明，细胞活力、增殖、附着和形态不受这些胶原蛋白抑制剂在阻断管形成和胶原蛋白生物合成的剂量下的存在的影响。D 609和GPA 1734还在体内血管生成模型系统中抑制响应SIKVAV的内皮细胞浸润。
结论
这些结果表明，新合成的胶原蛋白是表达用于管形成的内皮细胞表型的先决条件，并且阻止胶原蛋白生物合成抑制体内管形成和血管生成。
BACKGROUND
The formation of a basement membrane is the last step in the development of a new blood vessel. Matrigel, a laminin-rich reconstituted basement membrane matrix induces the differentiation of endothelial cells into capillary-like structures.
EXPERIMENTAL DESIGN
The effect of inhibitors of basement membrane collagen synthesis, tricyclodecan-9-yl xanthate (D609) and 8,9-dihydroxy-7-methyl-benzo[b] quinolizinium bromide (GPA 1734), was investigated on endothelial cell tube formation on Matrigel in vitro and in an angiogenesis assay in C57 black mice in vivo.
RESULTS
D609 and GPA 1734 caused a dose-dependent decrease in tube formation in vitro with complete inhibition at 50 micrograms/ml for D609 and 15 micrograms/ml for GPA 1734. The inhibitory effect on capillary tube formation by both agents was reversible. Tube formation correlated well with collagenous protein biosynthesis. Parallel studies on endothelial cells cultured on plastic indicate that cell viability, proliferation, attachment, and morphology were not affected by the presence of these collagen inhibitors at doses that blocked tube formation and collagen biosynthesis. D609 and GPA 1734 also inhibited endothelial cell infiltration in response to SIKVAV in an in vivo angiogenesis model system.
CONCLUSIONS
These results indicate that newly synthesised collagen is a prerequisite for expression of the endothelial cell phenotype for tube formation and that prevention of collagenous protein biosynthesis inhibits tube formation and angiogenesis in vivo.