Somatostatin gene transfer and expression in endothelial cells.
Somatostatin gene transfer and expression in endothelial cells.
复制标题
生长抑素基因在内皮细胞中的转移和表达。
DOI：
10.1016/s0741-5214(98)70278-2
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发表时间：
1998
影响因子：
4.3
通讯作者：
Stanley,JC
中科院分区：
文献类型：
--
作者：
Sarkar,R;Finniss,S;Dickinson,CJ;Stanley,JC
目的生长抑素的抗增殖和抗分泌作用在临床上有许多潜在的用途。逆转录病毒基因转移生长抑素的内皮细胞是一个潜在的手段，局部交付这种肽到特定的血管床。本研究旨在确定是否转导的内皮细胞（ECs）可以产生和后处理生长抑素.MethodsCultured犬静脉，大鼠主动脉，和大鼠微血管内皮细胞转染逆转录病毒含有人生长抑素cDNA或控制β-半乳糖苷酶基因。总的和异构体生长抑素生产和β-半乳糖苷酶的表达的均匀性进行了分析，生长抑素生产EC proliferation.ResultsSomatostatin-transduced犬静脉EC，但不是大鼠EC，产生约10倍的总生长抑素为对照转染EC（450 ± 32 vs 49 ± 10 pmol/L，p < 0.05）。生长抑素的主要亚型是生长抑素-14。生长抑素的生产是稳定的通过，并没有损害犬内皮细胞的生长。大鼠内皮细胞产生生长抑素的失败与β-半乳糖苷酶的不均匀表达相关，这表明启动子沉默是负责失败的转基因expression.ConclusionRetroviral基因转移生长抑素犬内皮细胞的结果在生产生理相关浓度的生物活性生长抑素。EC生长抑素的产生存在显著的种属差异，启动子沉默是基因表达失败的潜在机制。使用逆转录病毒将生长抑素转移到内皮细胞的基因治疗策略可能允许生长抑素递送到血管系统的焦点区域。（J Vasc Surg 1998;27：955-62.）
PurposeThe antiproliferative and antisecretory effects of somatostatin have many potential uses in the clinical setting. Retroviral gene transfer of somatostatin to endothelium is a potential means of local delivery of this peptide to specific vascular beds. This investigation was designed to determine whether transduced endothelial cells (ECs) could produce and post-translationally process somatostatin.MethodsCultured canine venous, rat aortic, and rat microvascular ECs were transfected with retroviruses containing a human somatostatin cDNA or a control β-galactosidase gene. Total and isoform somatostatin production and uniformity of β-galactosidase expression were analyzed, as were the effects of somatostatin production on EC proliferation.ResultsSomatostatin-transduced canine venous ECs, but not rat ECs, produced approximately 10 times as much total somatostatin as did control-transfected ECs (450 ± 32 vs 49 ± 10 pmol/L, p < 0.05). The predominant isoform of somatostatin produced was somatostatin-14. Production of somatostatin was stable with passage and did not impair the growth of canine ECs. The failure of rat ECs to produce somatostatin correlated with nonuniform expression of β-galactosidase, suggesting that promoter silencing was responsible for failure of transgene expression.ConclusionRetroviral gene transfer of somatostatin to canine ECs results in the production of physiologically relevant concentrations of biologically active somatostatin. Significant species differences exist in EC production of somatostatin, with promoter silencing being a potential mechanism of failure of gene expression. Gene therapy strategies using retroviral transfer of somatostatin to ECs may allow somatostatin delivery to focal areas of the vasculature. (J Vasc Surg 1998;27:955-62.)