Lou X J, Kwan H H, Prionas S D, Yang Z J, Lawn R M, Fajardo L F
Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California 94305, USA.
Exp Mol Pathol. 1998 Oct;65(2):53-63. doi: 10.1006/exmp.1998.2230.
Apolipoprotein(a) [apo(a)] contains a kringle domain(IV) homologous to that of angiostatin, a natural angiogenic inhibitor. Because of this structural similarity we suspected that apo(a) could be an inhibitor of angiogenesis. The possible role of apo(a) in microvascular proliferation was studied in an in vivo quantitative model, the disc angiogenesis system (DAS) and compared to angiostatin. Apo(a) and other test compounds were placed in the center of a polyvinyl alcohol foam disc that was implanted subcutaneously in mice. After 14 days, the disc was removed and vascular growth into the disc was measured. Apo(a) did not affect spontaneous vessel growth into the disc, while angiostatin suppressed this growth and basic fibroblast growth factor (bFGF) increased it. Additionally, apo(a) did not modify the vascular growth induced by bFGF. Transgenic mice expressing the human apo(a) gene were used to study the systemic effect of apo(a): neither an increase nor a decrease in vascular growth was detected. Our results suggest that apo(a) is unlikely to play a significant role in the control of angiogenesis. Furthermore, our experiments confirm the inhibitory effect of angiostatin not only on induced angiogenesis but also on baseline, spontaneous angiogenesis.
载脂蛋白(a)[apo(a)]含有一个与天然血管生成抑制剂血管抑素的kringle结构域(IV)同源的结构域。由于这种结构相似性，我们推测apo(a)可能是一种血管生成抑制剂。在一种体内定量模型——圆盘血管生成系统(DAS)中研究了apo(a)在微血管增殖中的可能作用，并与血管抑素进行了比较。将apo(a)和其他测试化合物置于植入小鼠皮下的聚乙烯醇泡沫圆盘的中心。14天后，取出圆盘并测量长入圆盘的血管生长情况。apo(a)不影响血管向圆盘的自发生长，而血管抑素抑制这种生长，碱性成纤维细胞生长因子(bFGF)则促进这种生长。此外，apo(a)不改变bFGF诱导的血管生长。利用表达人apo(a)基因的转基因小鼠研究apo(a)的全身作用：未检测到血管生长增加或减少。我们的结果表明，apo(a)不太可能在血管生成的控制中发挥重要作用。此外，我们的实验证实了血管抑素不仅对诱导性血管生成有抑制作用，而且对基线自发血管生成也有抑制作用。
