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

方法：喂饲0.5%胆固醇饲料的新西兰大白兔，球囊损伤后在髂外动脉置入Palmaz-Schatz支架。前列环素合成酶(PCS)基因(_PPCS，200 mg)通过脂质体转染法进入损伤动脉。结果：PCS基因转移后，(1)PGI2生成增加，(2)支架内皮化加快，(3)新生内膜形成明显减少。结论：PCs基因转移可促进动脉粥样硬化兔支架植入后血管内皮化，减少新生内膜形成，血管内皮生长因子可能在PCs基因转移的血管生成过程中起重要作用。大鼠动脉损伤后验证环氧合酶-2表达及COX-2衍生的前列腺素I2可刺激血管内皮细胞恢复…应用选择性COX-2抑制剂对大鼠颈动脉球囊损伤后COX-2和血管内皮生长因子的表达进行时间空间分析，评价COX-2在动脉形态计量学中的作用。结果：(1)PCS基因转移可显著增加PGI_2的生成，而JTE-522可抑制PGI_2的产生。(2)免疫组织化学分析显示，COX-2在血管内膜有较强的表达，并与血管内皮细胞的表达共存。(3)PCS基因转移促进了血管内皮细胞生长因子的表达，而JTE-522的表达减少。(4)PCS基因转移的血管内皮细胞的再生明显多于损伤血管。(5)PCS基因转移显著减少新生内膜的形成，而JTE-522则逆转了PCS基因转移的作用。结论：PCS基因转移可能通过上调COX-2诱导的血管内皮细胞表达和过量表达COX-2衍生的PGI2，从而促进血管内皮细胞的恢复，抑制新生内膜的形成。较少

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