Key result
Single intraluminal antisense PCNA ODN prevents neointimal formation in murine cardiac allografts versus control.
Why the study?
Does antisense PCNA ODN prevent allograft arterial intimal hyperplasia in murine cardiac allografts?
Does antisense PCNA ODN prevent allograft arterial intimal hyperplasia in murine cardiac allografts?
Antisense PCNA ODN delivery prevents cardiac allograft arteriosclerosis in a murine model, suggesting a potential therapeutic target for transplant vasculopathy.
Caution against clinical use in transplantation; leaves open PCNA targeting for human allograft vasculopathy research.
Cardiac allograft arteriosclerosis limits long-term survival of recipients and is characterized by intimal thickening comprised of proliferative smooth muscle cells. Proliferating-cell nuclear antigen (PCNA) plays a pivotal role in the cell cycle regulatory genes involved in smooth muscle cell proliferation. To test the hypothesis that antisense PCNA oligodeoxynucleotide (ODN) can prevent allograft arterial intimal hyperplasia, we performed single intraluminal delivery of the antisense or sense PCNA ODN or no transfer into murine cardiac allografts. DBA/2 murine hearts were transfected and transplanted into B10.D2 mice; the allografts were harvested 4 weeks later. Severe intimal thickening with enhanced expression of PCNA was observed in untransfected and sense PCNA ODN-treated allografts, whereas antisense PCNA ODN prevented neointimal formation.
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Suzuki et al. (2000) studied Cardiac allograft arteriosclerosis. Antisense PCNA oligodeoxynucleotide (ODN) vs. Sense PCNA ODN or no transfer was evaluated on Allograft arterial intimal hyperplasia. Single intraluminal delivery of antisense PCNA ODN prevented neointimal formation in murine cardiac allografts at 4 weeks compared to sense PCNA ODN or no transfer.
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