HGF as Angiogenic Factor and Therapeutic Approach

Title: HGF as Angiogenic Factor and Therapeutic Approach

Volume: 6 Issue: 2

Author(s): Yoshiaki Taniyama, Yasushi Takeya, Junya Azuma, Kazuma Iekushi, Fumihiro Sanada, Hiroshi Kusunoki, Keita Okayama, Nobutaka Koibuchi, Hiromi Rakugi and Ryuichi Morishita

Affiliation:

Keywords: Angiogenesis, gene therapy, peripheral artery disease (PAD), HGF, VEGF, hepatocyte growth factor, vascular endothelial growth factor, epithelial growth factor receptor, c-Met, SHIP-2, plasmid DNA transfer, Phase III clinical trial, EPCs, Cbl, ROS, VSMC, CLI, Ang II, fibroblast growth factor, epithelial growth factor, senescence, GTP binding rac1, Rutherford 5, ERK, Akt, ankle-brachial pressure index, QOL

Abstract: Hepatocyte growth factor (HGF) is a mesenchyme-derived pleiotropic factor which regulates cell growth, cell motility, and morphogenesis of various types of cells, and is thus considered a humoral mediator for morphogenic tissue interactions. Although HGF was originally identified as a potent mitogen for hepatocytes, it has also been identified as a member of angiogenic growth factors. Interestingly, the presence of its specific receptor, c-met, is observed in vascular cells and cardiac myocytes. On the other hand, recently, we demonstrated that HGF plasmid DNA transfer significantly improves the size of ulcer in patients with peripheral artery disease (PAD) at Phase III clinical trial, while vascular endothelial growth factor (VEGF) gene therapies for PAD at Phase III have not been succeeded yet. To further investigate this difference between HGF and VEGF, we showed that HGF but not VEGF improves the senescence EPC against oxidative stress through the inhibition of rac1. Moreover, we reported that HGF promotes SHIP-2 translocation from epithelial growth factor receptor (EGFR) to c-Met, and it would protect oxidative stress through EGFR degradation. By this anti-oxidative and anti-senescence effects of HGF would maintain the vessel so long in patients with PAD who receive much oxidative stress in real world. In this report, we discuss a potential therapeutic strategy using HGF in cardiovascular diseases.

Cite this article as:

Taniyama Yoshiaki, Takeya Yasushi, Azuma Junya, Iekushi Kazuma, Sanada Fumihiro, Kusunoki Hiroshi, Okayama Keita, Koibuchi Nobutaka, Rakugi Hiromi and Morishita Ryuichi, HGF as Angiogenic Factor and Therapeutic Approach, Current Signal Transduction Therapy 2011; 6 (2) . https://dx.doi.org/10.2174/157436211795660016