Endothelial cells are activated by angiopoeitin-1 gene transfer and produce coordinated sprouting in vitro and arteriogenesis in vivo |
| |
Authors: | Gluzman Zoya Koren Belly Preis Meir Cohen Tzafra Tsaba Adili Cosset Francois-Loic Shofti Rona Lewis Basil S Virmani Renu Flugelman Moshe Y |
| |
Institution: | MultiGene Vascular Systems Ltd, Lady Davis Carmel Medical Center, Haifa, Israel. |
| |
Abstract: | RATIONAL AND OBJECTIVES: Activation of fully differentiated vascular cells using angiogenic genes can lead to phenotypic changes resulting in formation of new blood vessels. We tested whether Ang-1 gene transfer to endothelial cells (EC) activates these cells. METHODS AND RESULTS: EC and SMC were transduced using retroviral or adenoviral vectors to produce Ang-1 or vascular endothelial growth factor (VEGF). EC Tie-2 receptor was phosphorilated by autologous secretion of Ang-1. Transduced EC and SMC sprouting capacity was tested using collagen embedded spheroids assay and capacity to produce arteriogenesis was tested in a hind limb model of ischemia. EC expressing Ang-1 in the presence of SMC expressing VEGF exhibited high levels of sprouting of the two cell types. Flow and numbers of arteries were increased after transduced cells implantation in vivo. CONCLUSIONS: Autologous secretion of Ang-1 by transduced EC resulted in Tie-2 activation and in the presence of SMC expressing VEGF resulted in coordinated sprouting in vitro and increase in flow and number of arteries in vivo. |
| |
Keywords: | Endothelial cells Smooth muscle cells VEGF Angiopoeitin-1 Arteriogenesis |
本文献已被 ScienceDirect PubMed 等数据库收录! |