Adenoviral gene transfer of basic fibroblast growth factor promotes angiogenesis in rat brain

Cerebral ischemic disease often causes morbidity and mortality, while the i nduction of new blood vessels is expected to provide a therapeutic effect i n this occlusive cerebrovascular disease. In this study, we utilized two re plication-deficient adenoviral vectors containing cDNA from basic fibroblas t growth factor (bFGF), a well-known angiogenic factor, and examined whethe r biological angiogenic activity of adenovirally gene-transferred bFGF coul d be observed in the rat brain. One vector contained native cDNA from bFGF without the secretory signal sequence and the other contained the same cDNA fused with an interleukin-2 secretory signal sequence. After ventricular a dministration of these viral vectors, gene-transferred cells demonstrated a high immunoreactivity against the anti-bFGF antibody and a remarkably high concentration of bFGF was detected in the cerebrospinal fluid. A semiquant itative analysis of angiogenic activity revealed that bFGF gene transfer in duced angiogenesis in normal rat brains, with a more pronounced angiogenic effect seen with the vector of a secreted form than with the vector without a secretory signal sequence. These results suggest that bFGF gene transfer using these adenoviral vectors might be useful for the treatment of ischem ic cerebrovascular disease.