Id1 Gene Transfer Confers Angiogenic Property on Fully Differentiated Endothelial Cells and Contributes to Therapeutic Angiogenesis
Id1 Gene Transfer Confers Angiogenic Property on Fully Differentiated Endothelial Cells and Contributes to Therapeutic Angiogenesis
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DOI：
10.1161/circulationaha.104.516898
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发表时间：
2005-11
期刊：
影响因子：
37.8
通讯作者：
Koichi Nishiyama;K. Takaji;Keiichiro Kataoka;Y. Kurihara;M. Yoshimura;A. Kato;H. Ogawa;H. Kurihara
中科院分区：
文献类型：
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作者：
Koichi Nishiyama;K. Takaji;Keiichiro Kataoka;Y. Kurihara;M. Yoshimura;A. Kato;H. Ogawa;H. Kurihara
背景-内皮祖细胞移植已被认为是治疗性血管重建的潜在策略。然而，有限的内源性细胞库和相关的技术困难构成了自体移植临床上的重要不利因素。在这项研究中，我们研究了Id1基因修饰的全分化内皮细胞(ECs)是否具有促进治疗性血管生成的潜力。方法和结果：通过仙台病毒载体将Id1基因导入人脐静脉内皮细胞。ID1刺激HUVECs迁移、增殖和毛细血管样管/索形成。此外，Annexin V流式细胞仪和TUNEL染色显示，Id1可减少血清剥夺诱导的HUVEC的凋亡。激光多普勒血流成像显示，高表达Id1基因的HUVECs移植后血流恢复加快，毛细血管密度增加，肢体保存率提高。组织化学分析显示，Id1高表达的人脐静脉内皮细胞移植后再生的血管网络中含有大量的人脐静脉内皮细胞，其中一些处于增殖状态。未转染的HUVECs也与Id1转染组的HUVECs融合，提示Id1的非细胞自主作用。最后，血管生成素-1在Id1过表达的人脐静脉内皮细胞中表达上调，并在功能上参与了Id1的体外血管生成作用。结论：Id1基因转移使HUVECs具有血管生成特性，有助于移植到缺血灶后的新生血管形成。移植ID1高表达的成熟内皮细胞可能成为治疗性血管生成的一种新的有用的策略。
Background— Transplantation of endothelial progenitor cells has been proposed as a potential strategy for therapeutic revascularization. However, the limited endogenous cell pool and the related technical difficulties constitute clinically important disadvantages to autologous transplantation. In this study we investigated whether fully differentiated endothelial cells (ECs) modified with gene transfer of Id1, a helix-loop-helix transcription factor involved in angiogenesis, have the potential to contribute to therapeutic angiogenesis. Methods and Results— The Id1 gene was transferred into human umbilical vein ECs (HUVECs) via a Sendai virus vector. Id1 stimulated migration, proliferation, and capillary-like tube/cord formation of HUVECs. In addition, Id1 reduced serum deprivation–induced HUVEC apoptosis, as shown by FACS analysis with annexin V and TUNEL staining. Transplantation of Id1-overexpressing HUVECs accelerated recovery of blood flow as evaluated by laser-Doppler perfusion imaging, increased capillary density, and improved the rate of limb salvage compared with the transplantation of control HUVECs. Histochemical analysis revealed that the regenerated vascular networks of limbs transplanted with Id1-overexpressing HUVECs contained numerous HUVECs, some of which were in a proliferative state. Untransfected HUVECs were also incorporated with Id1-transfected HUVECs, suggesting the noncell autonomous effect of Id1. Finally, angiopoietin-1 was upregulated in Id1-overexpressing HUVECs and functionally contributed to the in vitro angiogenic effect of Id1. Conclusions— Id1 gene transfer conferred HUVECs with an angiogenic property, contributing to neovascularization after transplantation into ischemic lesions. Transplantation of Id1-overexpressing mature ECs may serve as a novel and useful strategy for therapeutic angiogenesis.