Endogenous regulation of angiogenesis in the rat aorta model. Role of vascular endothelial growth factor.
Endogenous regulation of angiogenesis in the rat aorta model. Role of vascular endothelial growth factor.
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发表时间：
1997-11
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通讯作者：
Roberto F. Nicosia;Yuzhong J. Lin;Darcie Hazelton;XiaoHua Qian
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作者：
Roberto F. Nicosia;Yuzhong J. Lin;Darcie Hazelton;XiaoHua Qian
本研究旨在探讨血管内皮生长因子（VEGF）在大鼠主动脉血管新生模型中的作用。新鲜切割的主动脉环在无血清胶原凝胶培养中产生微血管增生。当从动物切除后10至14天将外植体包埋在胶原中时，血管生成减少至10%。条件培养基的免疫化学研究表明，VEGF分泌的主动脉培养物。VEGF的水平下降，在第二周的文化时，外植体变得静止和微血管停止生长。用外源性VEGF治疗静止的主动脉环刺激血管生成，并将微血管生长恢复到新鲜切割外植体培养物中观察到的值。大鼠主动脉血管形成胶原凝胶培养物的逆转录聚合酶链反应证实了选择性剪接亚型VEGF 165、VEGF 189和高亲和力VEGF受体flk-1的表达。逆转录-聚合酶链反应的大鼠血管内皮细胞衍生的细胞株证实了VEGF 165和VEGF 189在内皮细胞，平滑肌细胞，和成纤维细胞的存在。flk-1受体由内皮细胞表达，而不是由成纤维细胞或平滑肌细胞表达，这与VEGF的内皮靶向特异性一致。抗VEGF中和抗体可抑制70%的血管新生反应，而非免疫IgG则无此作用（P < 0.001）。这些发现为VEGF介导的自分泌/旁分泌调节大鼠主动脉模型中的血管生成提供了证据。
The purpose of this study was to investigate the role of vascular endothelial growth factor (VEGF) in the rat aorta model of angiogenesis. Freshly cut aortic rings generated microvascular outgrowths in serum-free collagen gel culture. Angiogenesis was reduced to 10% when the explants were embedded in collagen 10 to 14 days after excision from the animal. Immunochemical studies of conditioned medium demonstrated secretion of VEGF by the aortic cultures. Levels of VEGF decreased during the second week of culture when the explants became quiescent and microvessels stopped growing. Treatment of quiescent aortic rings with exogenous VEGF stimulated angiogenesis and restored microvascular growth to values observed in cultures of freshly cut explants. Reverse transcriptase polymerase chain reaction of vasoformative collagen gel cultures of rat aorta demonstrated the expression of the alternatively spliced isoforms VEGF165, VEGF189, and the high affinity VEGF receptor flk-1. Reverse transcriptase-polymerase chain reaction of rat aorta-derived cell strains confirmed the presence of VEGF165 and VEGF189 in endothelial cells, smooth muscle cells, and fibroblasts. The flk-1 receptor was expressed by endothelial cells but not by fibroblasts or smooth muscle cells, which is consistent with the endothelial target specificity of VEGF. The spontaneous angiogenic response of freshly cut aortic rings was inhibited by 70% with a neutralizing antibody against VEGF, whereas nonimmune IgG had no effect (P < 0.001). These findings provide evidence for a VEGF-mediated autocrine/paracrine regulation of angiogenesis in the rat aorta model.