EFFECT OF PGI_2 SYNTASE GENE TRANSFER ON NEOINTIMAL FORMATION AFTERAORTIC STENTING IN ANIMAL MODELS

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Atheromatous RabbitsMethods : New Zealand White Rabbits fed 0.5% cholesterol diet underwent balloon injury followed by Palmaz-Schatz stent implantation in the external iliac arteries. Prostacyclin synthase (PCS) gene (_PPCS, 200mg) was delivered into the injured arteries by lipotransfection method.Results : By PCS gene transfer, (1) the production of PGI2 was enhanced, (2) stent endothelialization was accelerated, and (3) neointimal formation was significantly reduced. Furthermore, _PPCS-tansfected vessels expressed much more vascular endothelial growth factor (VEGF) than control vessels.Conclusion : PCS gene transfer may accelerate re-endothelialization and attenuated neointimal formation after stent implantation in atheromatous rabbits and that VEGF may play an important role in angiogenic process of PCS gene transfer.Rats After Arterial InjuryTo test hypothesis that, in response to balloon injury, cyclooxygenase (COX)-2 expression and COX-2-derived PGI2 could stimulate VEGF to recov … More er vascular cell composition, we carried out chronospatial analysis ofCOX-2 and VEGF expression in balloon injured arteries and evaluated the role of COX-2 in arterial morphometry using selective COX-2 inhibitor.Methods : PCS gene was transfected to rat carotid arteries by lipotransfection method. A COX-2 inhibitor JTE-522 was given after balloon injury.Results : (1) PCS gene transfer significantly augmented PGI_2 production, while JTE-522 decreased this increase in PGI_2 production.(2) Immunohistochemical analysis revealed intense COX-2 expression in smooth muscle cells and regenerated endothelium on the neointima, which was colocalized with VEGF expression.(3) PCS gene transfer augmented VEGF expression, while JTE-522 decreased.(4) Regeneration of endothelium was significantly greater in the PCS gene transfected vessels than the injured vessels.(5) PCS gene transfer significantly reduced neointimal formation, while JTE-522 reversed the effect ofPCS gene transfer.Conclusion : PCS gene transfer may accelerate the endothelial recovery and inhibit neointimal formation, in part, via augmented VEGF expression by COX-2 induction and overproduced COX-2-derived PGI_2 in rat balloon-injured arteries. Less