ADENOVIRUS-MEDIATED GENE-TRANSFER OF BASIC FIBROBLAST GROWTH-FACTOR INDUCES IN-VITRO ANGIOGENESIS

To investigate the possibility of adenovirus-mediated gene transfer in the treatment of vascular occlusive diseases, we constructed a replic ation-deficient recombinant adenovirus vector coding for human basic f ibroblast growth factor (bFGF) and examined its effect on the prolifer ation and differentiation of vascular endothelial cells in vitro. Huma n umbilical vein endothelial cells (HUVECs) were successfully infected with high efficiency and expressed 18 kD protein which is immunoreact ive to anti-bFGF monoclonal antibody. This protein was accumulated mai nly in the nuclei of the cells, but was also detected in the culture m edium although the complimentary DNA (cDNA) did not contain the classi cal secreting signal sequence. The proliferation assay of HUVECs infec ted with bFGF-expressing adenovirus revealed a significant increase in cell number over control. Infection with this virus also enhanced tub ular formation of HUVECs on reconstituted basement membrane. Neovascul arization and the formation of collateral vessels play important roles in minimizing tissue damage in ischemic disorders. These results impl y that the use of bFGF-expressing recombinant adenovirus may be a suit able in vivo gene therapy for ischemic diseases. (C) 1997 Elsevier Sci ence Ireland Ltd.