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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Vascular wall maturation and prolonged angiogenic effect by endothelial-specific platelet-derived growth factor expression.
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Vascular wall maturation and prolonged angiogenic effect by endothelial-specific platelet-derived growth factor expression.

机译：血管壁的成熟和血管内皮细胞特有的内皮生长因子表达延长的血管生成作用。

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BACKGROUND: The implementation of angiogenic gene therapy at clinics is hindered by the transience of the therapeutic effect. Recruiting vascular wall smooth muscle cells, a process termed 'maturation', can stabilize newly formed vessels. OBJECTIVE: To induce angiogenesis followed by vessel maturation in a murine ischemic limb model by endothelial cell-specific promoter regulated expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB). METHODS: We constructed adenoviral vectors containing angiogenic factors VEGF and PDGF-B regulated by a modified preproendothelin-1 (PPE-1-3x) promoter and investigated their angiogenic effect in a murine ischemic limb model. Results: VEGF gene therapy increased perfusion and the vessel density in the limb shortly after expression with PPE-1-3x promoter or cytomegalovirus (CMV) promoter vectors, but only PPE-1-3xVEGF treatment exhibited a sustained effect. Expression of PDGF-B by PPE-1-3x promoter resulted in morphological maturation of the vasculature and further increased the perfusion, while nonspecific expression of PDGF-B with CMV promoter had no therapeutic effect. Regulation of dual therapy with VEGF and PDGF-B by PPE-1-3x promoter resulted in an early-onset, sustained angiogenic effect accompanied by vessel maturation. CONCLUSIONS: Systemic gene therapy with the angiogenic factors VEGF and PDGF-B under angiogenic- endothelial cell-specific regulation was effective in inducing functionally and morphologically mature vasculature.
机译：背景：在临床上，血管生成基因疗法的实施因其疗效的短暂性而受到阻碍。恢复血管壁平滑肌细胞的过程称为“成熟”，可以稳定新形成的血管。目的：通过内皮细胞特异性启动子调节血管内皮生长因子（VEGF）和血小板源性生长因子-BB（PDGF-BB）的表达，在鼠缺血肢体模型中诱导血管生成和随后的血管成熟。方法：我们构建了包含经修饰的前内皮素-1（PPE-1-3x）启动子调控的血管生成因子VEGF和PDGF-B的腺病毒载体，并研究了它们在鼠缺血性肢体模型中的血管生成作用。结果：使用PPE-1-3x启动子或巨细胞病毒（CMV）启动子表达后，VEGF基因治疗可增加灌注，并增加肢体血管密度，但只有PPE-1-3xVEGF治疗可显示持续作用。 PPE-1-3x启动子表达PDGF-B导致脉管系统形态成熟，并进一步增加了灌注，而CMV启动子非特异性表达PDGF-B没有治疗作用。 PPE-1-3x启动子对VEGF和PDGF-B双重疗法的调节导致早期发作，持续的血管生成作用以及血管成熟。结论：在血管生成内皮细胞特异性调控下，用血管生成因子VEGF和PDGF-B进行全身基因治疗可有效诱导功能和形态成熟的血管。

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