Clinical Application of Hepatocyte Growth Factor (HGF) to cardiovascular disease: Its molecular mechanisms and possibility of molecular therapy.

肝细胞生长因子（HGF）在心血管疾病中的临床应用：其分子机制和分子治疗的可能性。

基本信息

批准号：
13557065
负责人：
MORISHITA Yuichi
金额：
$ 7.23万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

1)Molecular mechanisms of HGF in regulation of vascular endothelial cells.This study demonstrated that HGF is not only growth factor but potent protector of endothelial cells. Endothelial cell death induced by high-glucose condition was inhibited by addition of HGF through the suppression of activation of caspase 3. Also, it was suggested that inhibition of cell death was mediated by up-regulation of bcl-xL and bcl-2.2)HGF-based gene therapy for ischemic diseases.We performed clinical gene therapy for peripheral arterial disease using HGF. Intramuscular injection of naked HGF plasmid is safe, feasible and can achieve successful improvement of ischemic limbs. Further clinical studies of alternative dosing regimens of gene therapy with randomized placebo-controlled trials will be required to define the efficacy of this therapy.Also, to evaluate the effect of HGF on ischemic heart disease, we employed NOGA system and demonstrated that gene transfer of HGF into myocardium resulted in increase in myocardial blood flow and decrease in ischemic area.3)Application of HGF to treatment for cerebral infarction.We demonstrated that gene transfer of HGF into ischemic brain resulted in suppression of neuron cell death and increase in blood supply as compared to that of control. Moreover, pre-treatment by trans-gene of HGF before Hgation decreased infracted area and improved behavior, suggesting its possibility of gene therapy for cerebral infarction.

1）HGF调节血管内皮细胞的分子机制。这项研究表明，HGF不仅是生长因子，而且是内皮细胞的有效保护因子。通过抑制caspase 3的激活抑制了由高葡萄糖疾病诱导的内皮细胞死亡。此外，也有人建议，通过bcl-XL和Bcl-XL和Bcl-2.2.2.2.2）介导基于缺血性疾病的HGF基因治疗的抑制作用。肌肉内注射裸HGF质粒是安全的，可行的，并且可以成功改善缺血性四肢。还需要对基因治疗的替代给药方案进行进一步的临床研究，并需要进行随机的安慰剂对照试验来定义这种疗法的功效。此外，以评估HGF对缺血性心脏病的影响，我们采用了NOGA系统，我们采用了NOGA系统，并证明了HGF转移到HGF中的肌电疗法中的基因流失方面的疗效，并导致了肌关闭疗法的疾病。我们证明，与对照相比，HGF转移到缺血性脑中的基因转移导致神经元细胞死亡和血液供应增加。此外，在Hgation之前，HGF的跨基因预处理降低了违规面积和改善的行为，这表明其基因治疗的脑梗塞可能性。