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

动物模型中 PGI_2 合酶基因转移对主动脉支架术后新内膜形成的影响

• 批准号: 12670658
• 负责人: MATSUI Hideo
• 金额: $ 0.96万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670658/
• 关键词: Aortic Stenting; Neointimal Formation; Gene Transfer

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

动脉粥样硬化兔方法：新西兰白色兔喂食0.5%胆固醇饲料，进行球囊损伤，然后在髂外动脉中植入Palmaz-Schatz支架。结果：前列环素合成酶基因（PPCS，200 mg）可促进PGI_2的生成，促进支架内皮化，减少新生内膜的形成。此外，转染PPCS的血管表达血管内皮生长因子（VEGF）明显高于对照血管。PCS基因转染可加速动脉粥样硬化兔支架植入后的再内皮化和减少新生内膜形成，VEGF在PCS基因转染的血管生成过程中可能起重要作用。环氧合酶（考克斯）-2表达和考克斯-2衍生的PGI 2可刺激VEGF恢复。 ...更多信息 方法：采用脂质体转染法，将PCS基因转染大鼠颈动脉，观察考克斯-2和VEGF在球囊损伤血管中的表达，并应用选择性考克斯-2抑制剂评价考克斯-2在血管形态计量学中的作用。结果：（1）PCS基因转移明显增加了PGI 2的产生，而JTE-522则抑制了PGI 2的产生。球囊损伤后给予考克斯-2抑制剂JTE-522。(2)免疫组化分析显示考克斯-2在新生内膜的平滑肌细胞和再生内皮细胞中有强烈的表达，并与VEGF表达共存。(3)PCS基因转移增加VEGF表达，而JTE-522降低。(4)PCS基因转染血管的内皮再生明显大于损伤血管。(5)结论：PCS基因转染可促进球囊损伤大鼠血管内皮的修复，抑制新生内膜的形成，其机制可能与诱导考克斯-2表达VEGF和过量产生考克斯-2衍生的PGI_2有关。少

项目成果

Osanai, H: "Ascorbic acid improves postischemic vasodilatation impaired by infusion of soybean oil into canine iliac artery"Journal of Cardiovascular Pharmacology. 36. 687-692 (2000)

Osanai，H：“抗坏血酸改善因将大豆油注入犬髂动脉而受损的缺血后血管舒张”《心血管药理学杂志》。

Okumura, K: "Beneficial effect of quinapril in patients with angiotensin-converting enzyme D allele after coronary stenting"Atherosclerosis. 159. 527-528 (2001)

Okumura, K：“喹那普利对冠状动脉支架置入术后血管紧张素转换酶 D 等位基因患者的有益作用”动脉粥样硬化。

Hayakawa, M.: "Simultaneous intravascular two-dimensional plus Doppler ultrasound ,is useful for evaluation of postischemic vasodilatation"Hypertension Research. 29. 331-338 (2000)

Hayakawa, M.：“同时血管内二维加多普勒超声，对于评估缺血后血管舒张非常有用”高血压研究。

Yamada, M: "Prostacyclin synthase gene transfer modulates cyclooxygenase-2-derived prostanoid syntheseis and inhibits neointimal formation in rat balloon-injured arteries"Arteriosclerosis, Thrombosis, and Vascular Biology. 22. 256-262 (2002)

Yamada, M：“前列环素合酶基因转移调节环氧合酶 2 衍生的前列腺素合成并抑制大鼠球囊损伤动脉中的新内膜形成”动脉硬化、血栓形成和血管生物学。

Okumura, K.: "Beneficial effect of quinapril in patients with angiotensin-conyerting enzyme D allele after coronary stenting"Atherosclerosis. 159. 527-528 (2001)

Okumura, K.：“喹那普利对冠状动脉支架置入术后血管紧张素转交酶 D 等位基因患者的有益作用”动脉粥样硬化。