Platelet-derived Endothelial Cell Growth Factor Gene Therapy for Arterial Intimal Thickening.

血小板源性内皮细胞生长因子基因治疗动脉内膜增厚。

• 批准号: 17591465
• 负责人: YAMADA Narihisa
• 金额: $ 2.3万
• 依托单位: 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591465/
• 关键词: PD-ECGF; atherosclerosis; Intimal Thickening; gene therapy; 血小板有来内皮細胞成長因子

TP/PD-ECGF has a chemotactic, but not a proliferative, effect on endothelial cells. Although TP/PD-ECGF has no mitogenic effect on endothelial cells, such as that of vascular endothelial growth factor. Taking these observations together with our previous in vivo study into account, we believe that TP/PD-ECGF has a strong angiogenic effect. However, the effect of TP/PD-ECGF on other types of vascular cells, especially VSMCs, required further consideration.2-French balloon catheters were inserted into the aorta of male rats through the right external carotid artery, and angioplasty of the right common carotid artery was performed by retracting the balloon catheter 3 times. A chitosan hydrogel containing pCIhTP/PD-ECGF or pCILacZ (pCI plasmid vector encoding TP/PD-ECGF gene or LacZ gene) was applied around the common carotid artery for gene delivery. Rats were killed 14 days later for measurement of neointima formation.X-gal staining revealed that chitosan hydrogel induced strong gene expression in the adventitia and vascular wall, and neointimal formation was significantly reduced in TP/PD-ECGF-treated rats 14 days after arterial injury. Immunohistochemical staining for smooth muscle cell arufa-actin demonstrated that neointima is composed predominantly of VSMCs in the pCI/LacZ treated groups, but there were fewer VSMCs in the pCIhTP group.These effects of TP/PDECGF indicate an ability to decrease neointimal smooth muscle cell proliferation and migration, which are therapeutically important because of their role in reducing neointimal mass in occlusive vascular diseases and inhibiting further neointimal growth.

TP/PD-ECGF对内皮细胞具有趋化作用，但不具有增殖作用。虽然TP/PD-ECGF对内皮细胞无促有丝分裂作用，如血管内皮生长因子。考虑到这些观察结果以及我们之前的体内研究，我们认为TP/PD-ECGF具有很强的血管生成作用。然而，TP/PD-ECGF对其他类型的血管细胞，特别是VSMCs的影响，需要进一步的研究。2-法国球囊导管插入到雄性大鼠的主动脉通过右颈外动脉，和右颈总动脉血管成形术进行了收缩球囊导管3次。将含有pCIhTP/PD-ECGF或pCILacZ（编码TP/PD-ECGF基因或LacZ基因的pCI质粒载体）的壳聚糖水凝胶施加在颈总动脉周围用于基因递送。X-gal染色显示，壳聚糖水凝胶可诱导血管外膜和血管壁基因表达增强，TP/PD-ECGF治疗组大鼠动脉损伤后14 d新生内膜形成明显减少。平滑肌细胞arufa-actin的免疫组化染色显示，在pCI/LacZ处理组中新生内膜主要由VSMCs组成，而在pCIhTP组中VSMCs较少。其在治疗上是重要的，因为它们在减少闭塞性血管疾病中的新生内膜质量和抑制进一步的新生内膜增生中起作用。增长

项目成果

Platelet-derived endothelial cell growth factor gene therapy for limb ischemia.

• DOI: 10.1016/j.jvs.2006.07.051
• 发表时间: 2006-12
• 期刊: Journal of vascular surgery
• 影响因子: 4.3
• 作者: N. Yamada;Wei Li;A. Ihaya;Tetsuya Kimura;K. Morioka;Takahiko Uesaka;A. Takamori;M. Handa;S. Tanabe;Kuniyoshi Tanaka