The fluctuating phenotype of the lymphohematopoietic stem cell with cell cycle transit

When damaged by hydrogen peroxide, peripheral blood lymphocytes undergo cell death by apoptosis in the absence of internucleosomal DNA cleavage, while, in the same cells, other apoptosis-inducing treatments bring DNA cleavage to completion. However, the formation of internucleosomal DNA fragments is readily obtained if cells are pretreated with a divalent metal chelator, TPEN, at micromolar concentrations. Since the coadministration of equimolar zinc concentrations abrogates the formation of the ladder, a zinc-inhibitable endonucleolytic activity is accounted for the effect. Most notably, subtraction of zinc ions does not increase the percentage of cells undergoing apoptosis, but rather results in a rescue from death.     

Sustained reduction of neointima with c-myc antisense oligonucleotides in saphenous vein grafts

BACKGROUND: Treatment of saphenous veins with c-myc antisense oligomers during preparation for grafting reduces medial cellular proliferation and macrophage infiltration, and preserves medial smooth muscle content at 3 days. Accordingly, the purpose of this study was to examine whether c-myc antisense oligomers have an impact on late vein graft remodeling. METHODS: Sixty-two pigs underwent unilateral saphenous vein-carotid artery interposition grafting. Harvested veins were incubated either in saline (control group) or 20-micromol/L or 200-micromol/L concentrations of c-myc antisense oligomers (treated groups) for 30 minutes intraoperatively. Three months after surgery, vein graft histology was assessed. RESULTS: Forty-five of 62 randomized animals survived the experiment; no differences in animal survival or graft patency among the groups were observed (p = NS, chi2). C-myc antisense oligomers significantly decreased neointimal and wall thickness, as well as increased lumenal index, in treated groups (p<0.04, p<0.03, and p<0.001, respectively, analysis of variance). In contrast, there was no difference in medial thickness or perivascular wound healing. CONCLUSION: Intraoperative treatment of saphenous veins with c-myc antisense oligomers decreased neointimal formation at 3 months after grafting. In conjunction with our previous reports, these findings suggest that early inhibition of cellular proliferation and inflammatory infiltration results in a sustained reduction in neointimal formation and favorable graft remodeling.