Angiogenic Therapy for Severe Ischemic Limb with Platelet-derived Endothelial Cell Growth Factor Gene

诱导血管生成反应以增强侧支血管发育是治疗血管闭塞性疾病的一种有前途的方法，这一概念被称为“治疗性血管生成”。为有效地形成侧支血管，目前研究最多的方法是局部注射血管生成因子，如血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）等，血小板源性内皮生长因子（PD-ECGF）与胸苷磷酸化酶（TP）相同;催化胸苷可逆磷酸解为胸苷2 '-脱氧-D-核糖-1-磷酸。PD-ECGF在体内具有促血管生成活性和内皮细胞趋化性，本研究检测了编码人全长PD-ECGF互补DNA的哺乳动物表达质粒载体在兔慢性缺血后肢中的有效性。我们发现，注射PD-ECGF基因引起的小牛血压比，血管造影评分和平滑肌细胞（SMC）阳性血管密度的改善，这是显着大于LacZ组和生理盐水组。这些结果提示PD-ECGF可能是基因治疗性血管新生治疗严重缺血肢体的一个有影响的候选基因。

Induction of angiogenic reactions to enhance collateral vessel development is a promising approach for the treatment of vascular occlusive disease, and this concept has been termed "therapeutic angiogenesis". A variety of procedures have been presented for the effective development of collateral vessels, and the most widely studied strategy is local delivery of angiogenic growth factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and others.Platelet-derived endothelial growth factor (PD-ECGF) is also identical to thymidine phosphorylase (TP); catalyze the reversible phoshorolysis of thymidine to thymidine 2'-deoxy-D-ribose-1-phosphate. PD-ECGF has been shown to process angiogenic activity in vivo and chemotaxis of endothelial cells.This study examine the effectiveness of delivery a mammalian expression plasmid vector encoding human full length PD-ECGF complementary DNA in the chronic ischemic hind limb of rabbit. We found that injecting of PD-ECGF gene induced improvement of calf blood pressure ratio, angiographic score, and smooth muscle cell (SMC)-positive vessel density, which were significantly greater than LacZ group and saline group. These findings suggested that PD-ECGF might be an influential candidate gene for gene therapeutic angiogenesis to severe ischemic limb.