Angiogenic therapy for Chronic Ischemic Myocardium with Platelet-derived Endothelial Cell Growth Factor Gene in aDog Model

狗模型中血小板源性内皮细胞生长因子基因对慢性缺血心肌的血管生成治疗

• 批准号: 12671303
• 负责人: CHIBA Yukio
• 金额: $ 2.43万
• 依托单位: Fukui Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671303/
• 关键词: PD-ECGFAT; angiogenesis; schemic myocardium; apptosis; 遺伝子治療; apoptosis; pCI vector; platelet-derived endothelial cell growth factor; 虚血性心疾患

Angiogenesis is a promising novel therapeutic strategy to provide new venues for blood flow in patients with severe ischemic heart arid peripheral vascular disease, who are not candidates for standard revascularization strategies.Platelet-derived endothelial cell gro\yth factor (PD-ECGF) is also identical to thymidine phosphorylase (TP), catalyze the reversible phosphorolysis of thymidine to thymine and 2'-deoxy-D-ribose-1-phosphate. PD-ECGFfTP has been shown to possess angiogenic activity in and confers resistance to apoptosis induced by hypoxia.This study examine the effectiveness of delivery a mammalian expression plasmid vector encoding human full length PD-ECGF/TP complementary DNA in the chronic canine ischemic myocardium. We found that injecting of PD-ECGF/TP gene not only induced angiogenesis, myocardiac function improvement, but also inhibited the apoptosis of the myocardial cells. The platelet-derived endothelial cell growth factor may be a influential candidate gene for gene therapeutic angibgenesis.

血管生成是一种有前途的新型治疗策略，可为不适合标准血运重建策略的严重缺血性心脏和周围血管疾病患者的血流提供新的场所。血小板源性内皮细胞生长因子（PD-ECGF）也与胸苷磷酸化酶（TP）相同，催化胸苷的可逆磷酸解 胸腺嘧啶和2'-脱氧-D-核糖-1-磷酸。 PD-ECGFfTP 已被证明具有血管生成活性，并赋予对缺氧诱导的细胞凋亡的抵抗力。本研究检查了在慢性犬缺血性心肌中递送编码人全长 PD-ECGF/TP 互补 DNA 的哺乳动物表达质粒载体的有效性。我们发现注射PD-ECGF/TP基因不仅可以诱导血管生成，改善心肌功能，而且可以抑制心肌细胞的凋亡。血小板源性内皮细胞生长因子可能是基因治疗性血管生成的一个有影响力的候选基因。