Endothelial cells are activated by angiopoeitin-1 gene transfer and produce coordinated sprouting in vitro and arteriogenesis in vivo.
OBJECTIVE
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.


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.
Gluzman
Zoya
Z
MultiGene Vascular Systems Ltd, Lady Davis Carmel Medical Center, Haifa, Israel.
Koren
Belly
B
Preis
Meir
M
Cohen
Tzafra
T
Tsaba
Adili
A
Cosset
Francois-Loic
FL
Shofti
Rona
R
Lewis
Basil S
BS
Virmani
Renu
R
Flugelman
Moshe Y
MY
D000256:Adenoviridae / Q000235:genetics; D042683:Angiopoietin-1 / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D001158:Arteries / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D018076:DNA, Complementary / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D012190:Retroviridae / Q000235:genetics; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042683:Angiopoietin-1; D018076:DNA, Complementary; D042461:Vascular Endothelial Growth Factor A