Gene transfer of antisense bFGF (ASbFGF) reduces bFGF expression and suppresses arterialized vein graft (VG) intimal hypeiplasia while promoting medial hypertrophy. The goal of this study was to determine if the outcome was a result of an altered balance between cellular (SMC) proliferation and apoptosis. Methods: Rabbit veins were infected with adenovirus encoding ASbFGF or lacZ (1×1010pfu/ml). Non viral Controls were treated with saline (PBS). Arterialized VGs were harvested 4, 7 and 21 days after gene transfer and grafting. Proliferating cell nuclear antigen (PCNA) immunohistochemistry served to quantify and locate SMC replication. Proliferative indices (PI) were compared by ANOVA. VGs were examined for apoptosis by DNA strand break assay (TUNEL). Results: PCNA: At 4 days all VGs had PCNA-positive SMCs adjacent to the lumen. By day 7, the forming neointima of the lacZ and PBS treated Control grafts remained PCNA+. In contrast, the ASbFGF treated VGs shed the neointima by day 7 and displayed medial and adventitial proliferative activity. At 3 weeks the ASbFGF treated VGs snowed a significantly lower total graft wall PI man Controls: ASbFGF=0.06, lacZ=0.16, PBS=0.19, P<0.005. At three weeks, PCNA-positive SMCs were localized to the thickened neointima of Control grafts. TUNEL: At 4 days ASbFGF treated VGs showed evidence of apoptosis in the majority of perilumenal cells while Control lacZ and PBS) grafts had few apoptotic cells. By 3 weeks all VGs were TUNEL negative. Conclusion: The results suggest that interruption of endogenous bFGF activity in arterialized VGs alters remodeling by promoting early apoptosis of the neointima with compensatory medial hypertrophy during the first three weeks following engraftment.
|Original language||English (US)|
|State||Published - Mar 20 1998|
All Science Journal Classification (ASJC) codes
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology