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

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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.