Riber Sara Schødt, Ali Mulham, Bergseth Sara Hveding, Stubbe Jane, Stenger Michael, Behr-Rasmussen Carsten, Lindholt Jes Sanddal
Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Denmark.
Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Denmark.
Ann Med Surg (Lond). 2017 Jun 15;20:26-31. doi: 10.1016/j.amsu.2017.06.017. eCollection 2017 Aug.
Abdominal aortic aneurysm (AAA) is a common disease with a high mortality. Many animal models have been developed to further understand the pathogenesis of the disease, but no large animal model has been developed to investigate the autoimmune aspect of AAA formation. The aim of this study was to develop a large animal model for abdominal aortic aneurysm induction through autoimmunity by performing sheep-to-pig xenotransplantation.
Six pigs underwent a xenotransplantation procedure where the infrarenal porcine aorta was replaced by a decellularized sheep aorta. In the following 47 days, the AP-diameter of the xenografts was measured using ultrasound once a week. All xenografts were harvested for histological analyses.
All the xenografts formed aneurysms with a mean increase in AP-diameter of 80.98 ± 30.20% (p < 0.005). The ultrasound measurements demonstrated a progressive aneurysmal expansion with no sign of halting towards the end of the follow-up period. Histology showed destruction of tunica media and the elastic tissue, neointimal hyperplasia, adventitial thickening with neovascularization, infiltration of lymphocytes and granulocytes, and in some cases intramural haemorrhaging.
We developed a novel large animal AAA model by infrarenal aortic sheep-to-pig xenograph transplantation resulting in autoimmune AAA induction with continuously progressive aneurysmal growth. This model can be used to provide a better understand the autoimmune aspect of AAA formation in large animals.
腹主动脉瘤(AAA)是一种常见疾病,死亡率很高。已经建立了许多动物模型以进一步了解该疾病的发病机制,但尚未开发出大型动物模型来研究AAA形成的自身免疫方面。本研究的目的是通过进行羊到猪的异种移植,开发一种通过自身免疫诱导腹主动脉瘤的大型动物模型。
六只猪接受了异种移植手术,用去细胞羊主动脉替换肾下腹主动脉。在接下来的47天里,每周一次使用超声测量异种移植物的前后径。所有异种移植物均进行组织学分析。
所有异种移植物均形成动脉瘤,前后径平均增加80.98±30.20%(p<0.005)。超声测量显示动脉瘤呈进行性扩张,在随访期结束时没有停止的迹象。组织学显示中膜和弹性组织破坏、新生内膜增生、外膜增厚伴新生血管形成、淋巴细胞和粒细胞浸润,在某些情况下还有壁内出血。
我们通过肾下腹主动脉羊到猪的异种移植建立了一种新型大型动物AAA模型,导致自身免疫性AAA诱导,动脉瘤持续进行性生长。该模型可用于更好地了解大型动物AAA形成的自身免疫方面。