Therapeutic Angiogenesis Using HGF Plasmid
ANNALS OF VASCULAR DISEASES
Authors: Sanada, Fumihiro; Fujikawa, Tatsuya; Shibata, Kana; Taniyama, Yoshiaki; Rakugi, Hiromi; Morishita, Ryuichi
Abstract
Hepatocyte growth factor (HGF) is secreted from stromal and mesenchymal cells, and its receptor cMet is expressed on various types of cells such as smooth muscle cells, fibroblast, and endothelial cells. HGF stimulates epithelial and endothelial cell proliferation, motility, and morphogenesis in a paracrine and autocrine manner, organizing multi-step of angiogenesis in many organs. In addition, HGF is recognized as a potent anti-inflammatory and anti-fibrotic growth factor, which has been proved in several animal studies, including neointimal hyperplasia and acute myocardial infarction model in rodent. Thus, as compared to other angiogenic growth factors, HGF exerts multiple effects on ischemic tissues, accompanied by the regression of tissue inflammation and fibrosis. These data suggest the therapeutic potential of the HGF for peripheral artery disease as it being accompanied with chronic tissue inflammation and fibrosis. In the present narrative review, the pleiotropic action of the HGF that differentiates it from other angiogenic growth factors is discussed first, and later, outcomes of the human clinical study with gene therapy are overviewed.
Efficacy of Ultrasound Microbubble-HGF Complex for Treating Hepatic Fibrosis and its Relation with Perfusion Weighted Imaging
PAKISTAN JOURNAL OF ZOOLOGY
Authors: Zhang, Shou-Hong; Zhang, Ying; Wen, Kun-Ming; Wu, Wei; Li, Wen-Yan
Abstract
We explored the feasibility of treating liver fibrosis with human Hepatocyte Growth Factor (HGF) carried by biotinylated ultrasound microbubbles plus biotinlated cationic nano-liposome composites (Bio-MB+Bio-CNLP) in bile duct-ligated (BDL) rats. In addition, we investigated the staging of hepatic fibrosis by using Perfusion-Weighted Imaging (PWI). We established a BDL rat model of hepatic fibrosis. HGF carrier was administered through tail-vein injections. The gene therapy efficacy was evaluated in vivo. Before and after treatment the rats were examined with MR-PWI. The perfusion parameters of PWl were compared with the fibrosis stage. The total fibrous tissue in the liver of rats treated with HGF was lower than that in control group. The time-signal intensity curve (TIC) peak of liver parenchyma of rats with hepatic fibrosis was characterized by a slow wash-in -out. A correlation was found between the perfusion parameters and the stage of fibrosis. As the stage of fibrosis increased, the wash-in and -out rates decreased progressively. The use of Bio-MB+Bio-CNLP is an effective and novel vector for gene delivery in vivo. Further, we confirm that HGF represents a valid liver anti-fibrotic molecule. PWI might be an effective method for quantifying the severity of liver fibrosis.