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

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14571259
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Faculty of Medical Sciences, University of Fukui
• Principal Investigator: KIMURA Tetsuya University of Fukui, Faculty of Medical Sciences, University of Fukui Hospital, Emergency Medicine, Instructor, 医学部附属病院, 助手 (50195369)
• Co-Investigator(Kenkyū-buntansha): LI Wei University of Fukui, Faculty of Medical Sciences, Department of Surgery II, Instructor, 医学部, 助手 (80362044) ; TERASAWA Syuuichi University of Fukui, University of Fukui Hospital, Faculty of Medical Sciences, Professor, 医学部附属病院, 教授 (30324164) ; TANAKA Kuniyoshi University of Fukui, Faculty of Medical Sciences, Department of Surgery II, Professor, 医学部, 教授 (70144251)
• Project Period (FY): 2002 – 2003
• Keywords: angiogenesis / severe ischemic limb / gene therapy / PD-ECGF / TP / LacZ / angiographic score / immunohistochemistry

Research Abstract

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.