Antisense inhibition of basic fibroblast growth factor induces apoptosis in vascular smooth muscle cells.

Antisense basic fibroblast growth factor gene transfer reduces early intimal thickening in a rabbit femoral artery balloon injury model

“…These data would suggest that the effect of Ad.ASbFGF gene delivery on the limitation of intimal thickening after balloon injury is not mediated by a significant inhibition of cellular proliferation, as seems to be the case when initial bFGF released by injured and dying cells is blocked by antibody, 3,6 but rather by induction of apoptosis and cellular demise. These findings are consistent with the in vitro data previously reported by Fox and Shanley 16 and suggest that sustained bFGF signaling is critical to the survival of vascular SMCs in vitro and in vivo. It would appear that loss of SMCs by apoptosis in the early phase leads to fewer cells actually proliferating (at a rate not significantly altered); therefore, there would be fewer cells depositing extracellular matrix, thereby limiting intimal thickening by 14 days after injury.…”

“…The Ad.ASbFGF recombinant adenovirus was constructed by replacement of the b-galactosidase cDNA with a 1.1 kb rat bFGF cDNA (in the antisense orientation) in the pAd.CMV lac Z shuttle vector, followed by homologous recombination with the E1, E3 deleted, human adenovirus serotype 5 mutant dl7001 in human embryonal kidney 293 cells, as previously described. 16 Rat and rabbit bFGF is approximately 90% homologous. 17 The control virus for all experiments was a replication-deficient recombinant adenoviral vector encoding the bacterial b-galactosidase reporter gene (gift of Dr. James Wilson, University of Pennsylvania).…”

Antisense basic fibroblast growth factor gene transfer reduces neointimal thickening after arterial injury

“…In addition, the SMC cultures infected with Ad.ASbFGF exhibit a dose-dependent reduction in survival compared with control cultures. 12 It is not known whether after arterial injury, newly synthesized bFGF contributes to cellular events, leading to intimal hyperplasia in vivo. To study the role of bFGF synthesized in vivo after arterial injury, we exposed the carotid artery to a recombinant adenovirus encoding ASbFGF RNA, delivered locally as a single dose at the time of injury.…”

Normal Human Melanocytes That Express a bFGF Transgene Still Require Exogenous bFGF for Growth In Vitro

“…Of greater significance are reports that suggest that bFGF may protect cells from apoptosis. bFGF has been shown to protect endothelial cells and vascular smooth muscle cells from apoptosis induced by radiation or serum starvation, respectively (Fuks et al, 1994;Fox and Shanley, 1996), and the levels of intracellular bFGF expression in chronic lymphocytic leukemia cells correlated with the cells' resistance to apoptosis induced by chemotherapeutic drugs (Menzel et al, 1996). Melanoma cells may receive natural apoptotic stimuli through receptors for components of the extracellular matrix.…”