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

方法：采用0.5%胆固醇饮食的新西兰大白兔髂外动脉球囊损伤后植入Palmaz-Schatz支架。采用脂肪转染法将prostocyclinsynthase （PCS）基因（_PPCS, 200mg）送入损伤动脉。结果：PCS基因转染后，(1)PGI2生成增强，(2)支架内皮化加速，(3)内膜形成明显减少。此外，_ppcs转染的血管比对照血管表达更多的血管内皮生长因子（VEGF）。结论：动脉粥样硬化家兔支架植入术后，PCS基因转移可加速血管再内皮化，减轻血管内膜形成，VEGF可能在PCS基因转移血管生成过程中起重要作用。为了验证球囊损伤后，环氧化酶(COX)-2的表达和COX-2衍生的PGI2可以刺激血管内皮生长因子恢复的假设，我们对球囊损伤动脉中COX-2和VEGF的表达进行了时空分析，并使用选择性COX-2抑制剂评估了COX-2在动脉形态测量中的作用。方法：采用脂质转染法将PCS基因转染大鼠颈动脉。球囊损伤后给予COX-2抑制剂JTE-522。结果：(1)PCS基因转染显著提高了PGI_2的产量，而JTE-522则降低了PGI_2的产量。(2)免疫组化分析显示，COX-2在新生内膜的平滑肌细胞和再生内皮中表达强烈，并与VEGF表达共定位。(3) PCS基因转染使VEGF表达增强，而JTE-522表达降低。(4)转染PCS基因的血管内皮细胞的再生明显高于损伤血管。(5) PCS基因转染显著降低了新生内膜的形成，而JTE-522逆转了PCS基因转染的作用。结论：PCS基因转移可能通过诱导COX-2增强VEGF表达和过量产生COX-2衍生的PGI_2来促进大鼠球囊损伤动脉内皮细胞的恢复和抑制新生内膜的形成。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