Fan Yen LEE
Current Position
Attending Cardiothoracic and Vascular surgeon, Director of Advanced Therapy Program (Heart Transplantation and Ventricular Assist Device)
Kaohsiung Chang Gung Memorial Hospital, Chang Gung University
Research Forum Session

Topic: Angiogenesis and blood flow-augmenting role of tissue plasminogen activator in the ischemic limb in a murine model


The purpose of the study is to test the hypothesis that tissue plasminogen activator (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization from bone marrow to circulation in murine critical limb ischemia (CLI). We equally divided wild-type mice and tPA knock-out (tPA−/−) mice into groups (sham control, CLI, control-tPA and CLI-tPA). We found the circulating levels of EPCs (C-kit/CD31+, Sca-1/KDR+, CXCR4/CD34+) were lower in groups tPA−/− than in groups wild-type with or without CLI respectively, reversed after tPA treatment at 6 h and 18 h post-CLI, but decreased again 14 days after CLI in tPA−/− mice compared to those in wild-type between the respective groups. These findings indicate that the percentage of circulating c-Kit/CD31+cells was notably reduced in tPA−/− mice compared to that in the wild-type in both normal and ischemic conditions. In addition, the suppressed EPC levels in tPA−/− animals could be reversed after tPA treatment. Furthermore, laser doppler flowmetry showed a higher ratio of ischemic-to-normal blood flow in group of wild-type with CLI than the comparable tPA−/− group. We concluded tPA played an essential role in augmenting circulating EPCs, angiogenesis, and blood flow in the ischemic limb in a murine model.