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

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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