Novel clinical strategy for thoracic anerysm using intra/extra vascular stenting and molecular biological drug delivery system.

使用血管内/血管外支架和分子生物药物输送系统治疗胸廓动脉瘤的新临床策略。

• 批准号: 09470277
• 负责人: HIRATA Nobuaki
• 金额: $ 7.62万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470277/
• 关键词: aortic aneurysm; vascular stent; drug delivery system; HVJ-liposome; gene tranfer; minimally invasive surgery

Recently the number of patients with an aortic aneurysm has been growing with increasing population of old age. Operations such as graft replacement have so far been employed for treatment of an aortic aneurysm. but its clinical results are still not satisfactory in terms of both the operative mortality/morbidity and the postoperative quality of life. Thus it is important to develop a new strategy of minimally invasive approach for treatment of aortic aneurysm.The purpose of this study is to prevent progression of aortic aneurysm by using endovascular drug delivery system (DDS) and to develop less invasive surgical procedure by introducing an endoscopic extravascular stenl in addition to an intravascular stent. As a molecular biological DDS, a gene transfection using HVJ-liposome method was used There is no report about extravascularstent for treatment of aortic aneurysm, and thus, this clinical strategy using intra/extra vascular stent combined with a new DDS using gene transfection i … More s considered to be a novel approach.In the clinical study, the patients with a slight aneurysmal change in the aortic wall have been followad up in order to clarify and evaluate the factor of anerysmal formation. Encbvaseular stenting was performed in 4 patients with abdominal aortic aneurysm and 3 patients with thoracic aortic aneurysm with excellent results.In the basic study, human senescent cell-derived inhibitor (sdi)-1 gene was transfected into the vein graft using HVJ-liposome method in rabbit vein graft model. Single intraluminal incubation of human sdi-1 gene resulted in significant inhibition of neointimal formation after vein grafting, associated whth phenotypic change of VSMCs from neonatal to adult type.The correlation of the phenotypic modulation of smooth muscle cells in the process of neointima formation afer stent implation in rabbit aorta and leucine-rich small proteoglycans, decorin and biglycan, which are considered to participate in regulation of extracellular matrix accumulation in arterial intinal hyperplasia, is investigated. The biglycan and dccorin kinetics during neointima fomalion alter arterial injury are distinct ; biglycan synthesis correlates with the enbryonic smooth muscle cells, whereas decorin synthesis is accelerated by IL-1 beta secreted from macrophages accumulating in the injured areas in the late stage after the vascular injury.These results may promise to clarify the mechanism of progression of aortic aneurysm and may help to develop a novel strategy of DDS in corporation with intra/extra stenting for treatment of aortic aneurysm. Less

近年来，随着老年人口的增加，主动脉瘤患者的数量一直在增加。到目前为止，移植物置换等手术已被用于治疗主动脉瘤。但在手术死亡率/发病率和术后生活质量方面，其临床效果仍不令人满意。因此，开发一种新的微创方法治疗主动脉瘤具有重要意义。本研究的目的是通过使用血管内药物输送系统(DDS)预防主动脉瘤的进展，并通过在血管内支架的基础上引入内窥镜血管外狭窄来开发侵入性较小的外科手术方法。目前尚无血管外支架治疗主动脉瘤的报道，因此，本研究采用血管内/外支架联合基因转染法治疗主动脉瘤的临床策略为i…。更多的S被认为是一种新的方法。在临床研究中，对主动脉壁有轻微动脉瘤改变的患者进行了随访，以澄清和评估无瘤形成的因素。对4例腹主动脉瘤和3例胸主动脉瘤患者进行了血管内支架植入术，取得了良好的效果。在基础研究中，将人衰老细胞衍生抑制物(SDI)-1基因通过HVJ-脂质体法导入到兔移植静脉模型中。将人SDI-1基因单独腔内孵育，可显著抑制移植静脉移植后新生内膜的形成，并与血管内膜细胞表型由新生向成年型转变有关。本文研究了兔主动脉内支架植入后新生内膜形成过程中平滑肌细胞表型变化与富含亮氨酸的小分子蛋白多糖、核心蛋白聚糖和二聚糖之间的关系。在动脉损伤后新生内膜形成过程中，Biglycan和Dccorin的动态变化是不同的，Biglycan的合成与血管内的平滑肌细胞有关，而Decorin的合成则被血管损伤后晚期损伤区域的巨噬细胞分泌的IL-1β所加速。这些结果可能有助于阐明主动脉瘤的进展机制，并有助于开发DDS联合支架内或外支架治疗主动脉瘤的新策略。较少

项目成果

Yamakawa T,Bai H,Masuda J,Sawa Y,Shirakura R,Ogata J,Matsuda H: "Differential expression of proteoglycans bigycan and decorin during neointima formation after stent implantation in normal and atherosclerotic rabbit aortas." (submitted).

Yamakawa T、Bai H、Masuda J、Sawa Y、Shirakura R、Ogata J、Matsuda H：“正常和动脉粥样硬化兔主动脉支架植入后新内膜形成过程中蛋白聚糖双聚糖和核心蛋白聚糖的差异表达。”

Imagawa H,Kadoba K,Taniguchi K,Sawa Y,Takahashi T,Fukushima N,Yoneda M,Fujii Y,Nakahara K,Matsuda H: "Saccular aneurysm in the right-sided aorticarch : A successfully corrected case." J Vasc Surg. 25. 941-944 (1997)

Imakawa H、Kadoba K、Taniguchi K、Sawa Y、Takahashi T、Fukushima N、Yoneda M、Fujii Y、Nakahara K、Matsuda H：“右侧主动脉弓囊状动脉瘤：成功矫正的病例。”

Hiroshi Imagawa: "Saccular aneurysm in the right-sided aortic arch ; A successfully corrected case" Journal of vascular surgery. 25. 941-944 (1997)

今川浩：“右侧主动脉弓囊状动脉瘤；成功纠正的病例”血管外科杂志。

Bai H,Masuda J,Sawa Y,Nakano S,Shirakura R,SHimazaki Y,Ogata J,Matsuda H: "Neointima formation after vascular stent implantation : spatial and chronological distribution of smooth muscle cell proliferation and phenotypic modulation." Arterioscler Thromb.

Bai H，Masuda J，Sawa Y，Nakano S，Shirakura R，SHImazaki Y，Ogata J，Matsuda H：“血管支架植入后新内膜形成：平滑肌细胞增殖和表型调节的空间和时间分布。”

M.Nishimura: "Endorascular steut graft placement for patients with aortic anenrysm and end-organ dysfunetion" ASAIO Journal. Vol44, No.5. 511-515 (1998)

M.Nishimura：“主动脉瘤和终末器官功能障碍患者的血管内移植物放置”ASAIO 杂志。