Anghel Andrei, Mut-Vitcu Bogdan, Savu Lorand, Marian Catalin, Seclaman Edward, Iman Raluca, Neghina Adriana-Maria, Dragulescu Stefan I
Department of Biochemistry, "Victor Babes" University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Square, Timisoara, Romania,
Genomic Med. 2007;1(1-2):47-55. doi: 10.1007/s11568-007-9006-5. Epub 2007 May 25.
The present study focuses on the application of a therapeutic strategy in patients with chronic severe lower limb ischaemia using a plasmid vector encoding the vascular endothelial growth factor (phVEGF(165)). It has been shown that VEGF promotes neo-vascularization and blood vessel network formation and thus might have the ability to improve blood-flow at the level of the affected limbs. However, little information is available regarding the necessary level of expression of VEGF and its possible related adverse effects. We have subcloned VEGF ( 165 )isoform into pCMV-Script expression vector (Stratagene) under the control of the CMV promoter. Three patients with chronic ischaemia of the lower limb, considered as not suitable for surgical re-vascularization, received intramuscular injection with 0.5 ml saline solution containing 10(11) copies of VEGF ( 165 ) plasmid. The clinical evolution has been monitored by angiography and estimated by walking time on the rolling carpet (Gardner protocol). Two months after therapy, all three patients showed complete relief of rest pain, improvement of ischaemic ulcer lesions and increased walking distance on the rolling carpet most probably due to appearance of newly formed collateral vessels.
本研究聚焦于一种治疗策略在慢性严重下肢缺血患者中的应用，该策略使用编码血管内皮生长因子（phVEGF(165)）的质粒载体。已表明VEGF可促进新血管形成和血管网络构建，因此可能有能力改善患肢的血流。然而，关于VEGF的必要表达水平及其可能的相关不良反应的信息很少。我们已将VEGF(165)异构体亚克隆到受CMV启动子控制的pCMV-Script表达载体（Stratagene公司）中。三名被认为不适合手术血管重建的慢性下肢缺血患者，接受了肌肉注射含10(11)拷贝VEGF(165)质粒的0.5毫升盐溶液。通过血管造影监测临床进展，并根据在滚动地毯上的行走时间（加德纳方案）进行评估。治疗两个月后，所有三名患者均表现出静息痛完全缓解、缺血性溃疡病变改善以及在滚动地毯上行走距离增加，这很可能是由于新形成的侧支血管出现所致。
