THROMBOSPONDIN EXERTS AN ANTIANGIOGENIC EFFECT ON CORD FORMATION BY ENDOTHELIAL-CELLS INVITRO
THROMBOSPONDIN EXERTS AN ANTIANGIOGENIC EFFECT ON CORD FORMATION BY ENDOTHELIAL-CELLS INVITRO
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DOI：
10.1073/pnas.88.11.5026
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
SAGE, H
中科院分区：
文献类型：
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作者：
IRUELAARISPE, ML;BORNSTEIN, P;SAGE, H
内皮细胞对血管生成刺激的反应已被证明受到细胞外微环境的影响。 我们测试了血小板反应蛋白（一种细胞外基质蛋白）是否在体外调节内皮细胞自发形成索。 尽管继续增殖，分泌的血小板反应蛋白减少检测到在索含，与亚融合，培养物的主动脉和微血管内皮细胞。 与此趋势相一致，血小板反应蛋白的mRNA水平在主动脉中降低了16倍，在含有内皮索的微血管培养物中降低了60倍。 由于血小板反应蛋白被免疫定位于似乎与内皮索相关的纤维阵列，我们将抗血小板反应蛋白IgG添加到索形成培养物中以限制该过程中蛋白质的可用性。 在抗血小板反应蛋白抗体的存在下，脐带形成增加了33-50%。 这些结果表明，血小板反应蛋白是血管生成的抑制剂，在体外，并与其提出的作用，作为一个不稳定的内皮细胞局灶性接触和作为抑制剂的内皮细胞增殖。
The response of endothelial cells to angiogenic stimuli has been shown to be influenced by the extracellular microenvironment. We tested whether thrombospondin, an extracellular matrix protein, modulated the spontaneous formation of cords by endothelial cells in vitro. Despite continued proliferation, a decrease in secreted thrombospondin was detected in cord-containing, as compared with subconfluent, cultures of both aortic and microvascular endothelial cells. Consistent with this trend, mRNA levels of thrombospondin decreased by factors of 16 in aortic and 60 in microvascular cultures that contained endothelial cords. Since thrombospondin was immunolocalized to fibrillar arrays that appeared to be associated with endothelial cords, we added anti-thrombospondin IgG to cord-forming cultures to limit the availability of the protein during this process. In the presence of anti-thrombospondin antibodies, there was a 33-50% increase in cord formation. These results suggest that thrombospondin is an inhibitor of angiogenesis in vitro and are consistent with its proposed roles as a destabilizer of endothelial cell focal contacts and as an inhibitor of endothelial cell proliferation.