Iruela-Arispe M L, Bornstein P, Sage H
Department of Biological Structure, University of Washington, Seattle 98195.
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5026-30. doi: 10.1073/pnas.88.11.5026.
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.
内皮细胞对血管生成刺激的反应已被证明受细胞外微环境的影响。我们测试了细胞外基质蛋白血小板反应蛋白是否在体外调节内皮细胞索的自发形成。尽管细胞持续增殖，但与亚汇合的主动脉和微血管内皮细胞培养物相比，在含有细胞索的培养物中检测到分泌的血小板反应蛋白减少。与这一趋势一致，在含有内皮细胞索的主动脉培养物中，血小板反应蛋白的mRNA水平下降了16倍，在微血管培养物中下降了60倍。由于血小板反应蛋白免疫定位在似乎与内皮细胞索相关的纤维状阵列上，我们在形成细胞索的培养物中加入抗血小板反应蛋白IgG，以限制该蛋白在此过程中的可用性。在抗血小板反应蛋白抗体存在的情况下，细胞索形成增加了33%-50%。这些结果表明，血小板反应蛋白在体外是血管生成的抑制剂，这与其作为内皮细胞粘着斑去稳定剂和内皮细胞增殖抑制剂的作用一致。
