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

血小板源性内皮细胞生长因子基因治疗严重缺血性肢体

• 批准号: 14571259
• 负责人: KIMURA Tetsuya
• 金额: $ 1.79万
• 依托单位: Faculty of Medical Sciences, University of Fukui
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571259/
• 关键词: angiogenesis; severe ischemic limb; gene therapy; PD-ECGF; TP; LacZ; angiographic score; immunohistochemistry; 下肢虚血; 閉塞性動脈硬化症

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.

诱导血管生成反应以促进侧支血管发育是治疗血管闭塞疾病的一种很有前途的方法，这一概念被称为治疗性血管生成。为了有效地发育侧支血管，已经提出了各种方法，其中研究最广泛的策略是局部输送血管生成生长因子，如血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(BFGF)等。血小板衍生的内皮生长因子(PD-ECGF)也与胸苷磷酸化酶(TP)相同，催化胸苷的可逆光短解为胸苷2‘-脱氧-D-核糖-1-磷酸。PD-ECGF具有体内血管生成活性和血管内皮细胞的趋化作用。本研究检测了携带全长PD-ECGF互补DNA的哺乳动物表达载体在兔慢性缺血后肢的有效性。我们发现，注射PD-ECGF基因后，小牛血压比、血管造影评分和SMC阳性血管密度的改善均显著高于LacZ组和生理盐水组。提示PD-ECGF可能是严重缺血肢体基因治疗性血管生成的重要候选基因。

项目成果

Liw: "Role of MMPs and plasminogen activators in angiogenesis after transmyocardial laser revascularization in dogs"Am J Physiol Heart Circ Phsiol. 284(1). H23-H30 (2003)

Liw：“MMP 和纤溶酶原激活剂在狗经心肌激光血运重建后血管生成中的作用”Am J Physiol Heart Circ Phsiol。