Potential application of proangiogenic BPC 157 on peripheral artery disease through activation of VEGFR2 signaling pathway

• Main Authors: Ming Jer Hsieh, 謝明哲
• Other Authors: J. H. S. Pang
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/237478

博士 === 長庚大學 === 臨床醫學研究所 === 105 === Peripheral arterial occlusive disease (PAD) often results in chronic limb ischemia, poor wound healing, even limb amputation. With the advance of endovascular therapy, the clinical outcomes of these patients were more improved than before. However, still a lot of patients are in the end-stage of disease, which are called "no option". The therapeutic angiogenesis is a new strategy for these end-stage patients. BPC-157, a kind of pentadecapeptide, is composed of 15 amino acids (GEPPPGKPADDAGLV, M.W. 1419), which is stable in human gastric juice and no toxicity. It can be dissolved in water and no need carrier for its application. Experimentally BPC-157 is effective in not only variable gastrointestinal disease but also doxorubicine-induced heart failure, cell survival, and different wound healing. The main purpose of this study is to investigate the effect of BPC 157 in PAD. In rat model, we found BPC 157 could accelerate improvement of blood flow perfusion in ischemic hind-limb. The expression of VEGF and VEGFR2 were increased in those rats treated with BPC-157. In vitro study, we also found BPC-157 could promote VEGFR2 endocytosis and activate VEGFR2-Akt-eNOS signaling pathway in endothelial cell. It has been known that VEGFR2, carveolin-1 (CAV-1) and eNOS are in caveolae. As endothelial cell is in inactive status, eNOS is binding to CAV-1, which avoid eNOS phosphorylation by calmodulin. In this study, we found BPC 157 can enhance phosphorylation of Src and CAV-1 in endothelial cells. In addition, BPC 157 can dissociate eNOS and CAV-1 in co-immunoprecipitation study. We hope BPC-157 could be a potential drug for PAD therapy in the future.