Therapeutic induction of angiogenesis by direct myocardial administration of an adenovirus vector encoding human hepatocyte growth factor gene and its safety

• Published in: Chinese science bulletin 2004, Vol.49 (14), p.1464-1469
• Main Author: WU, Danli
• Format: Article
• Language: English
• Subjects: Adenoviruses; Angiogenesis; Angiography; Antibodies; Blood flow; Blood vessels; Chronic toxicity; Evaluation; Growth factors; Hepatocyte growth factor; Image analysis; Image processing; Ischemia; Microspheres; Myocardial infarction; Myocardium; Neutralization; Safety; Toxicity testing; Vascular diseases; 中和抗体; 冠状动脉粥样硬化; 基因治疗; 安全性; 心肌局部缺血; 矢量编码; 肝细胞生长因子; 血管生成; 重组体腺病毒
• ISSN: 1001-6538; 2095-9273; 1861-9541; 2095-9281
• DOI: 10.1360/04wc0161

After the study in vitro and in rats, we assessed further the effects and safety of local angiogen therapy using intramyocardial delivery of an adenovirus carrying hepatocyte growth factor gene (Ad-HGF) in a canine ischemia model. The angiogenic activity of Ad-HGF was evaluated from three aspects. First, the augmentation of collateral vessel development was assessed by angiography 30 d after surgery. The results showed that the density of collateral vessels in treated group was higher than that of control group. Secondly, infarct size was evaluated by TTC staining and image analysis. The results showed that the infarct size of treated group was smaller than that of control group. Thirdly, the myocardial regional blood flow was determined by the method of colored microspheres. The results showed that the blood flow recovered to the level before ligation in treated group, but that of the control group was lower than normal level. In addition, during the study of chronic toxicity, we tested the anti-adenovirus antibodies by neutralization method. The antibodies yielded after the fourth injection decreased slowly from peak level and disappeared 12 weeks after drug withdrawal. Overall, Ad-HGF can promote angiogenesis in ischemic myocardium and reduce infarct size. So this method may be considered as a therapeutic angiogenesis induction strategy for ischemic disease including myocardial infarction and peripheral artery disease. At the same time, Ad-HGF could induce the yield of anti-adenovirus antibodies to neutralize adenovirus, which may be the mechanism of adenovirus clearance.