Induction of autoimmune abdominal aortic aneurysm in pigs: A novel large animal model

Sara Schødt Riber*, Mulham Ali, Sara Hveding Bergseth, Jane Stubbe, Michael Stenger, Carsten Behr-Rasmussen, Jes Sanddal Lindholt

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Resumé

Background 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. Methods 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. Results 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. Conclusion 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.

OriginalsprogEngelsk
TidsskriftAnnals of Medicine and Surgery
Vol/bind20
Sider (fra-til)26-31
ISSN2049-0801
DOI
StatusUdgivet - aug. 2017

Fingeraftryk

Abdominal Aortic Aneurysm
Heterografts
Adventitia
Elastic Tissue
Autoimmunity
Hyperplasia
Growth

Citer dette

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title = "Induction of autoimmune abdominal aortic aneurysm in pigs: A novel large animal model",
abstract = "Background 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. Methods 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. Results 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. Conclusion 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.",
keywords = "Abdominal aortic aneurysm, Autoimmunity, Porcine model, Sheep-to-pig xenotransplantation",
author = "Riber, {Sara Sch{\o}dt} and Mulham Ali and Bergseth, {Sara Hveding} and Jane Stubbe and Michael Stenger and Carsten Behr-Rasmussen and Lindholt, {Jes Sanddal}",
year = "2017",
month = "8",
doi = "10.1016/j.amsu.2017.06.017",
language = "English",
volume = "20",
pages = "26--31",
journal = "Annals of Medicine and Surgery",
issn = "2049-0801",
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Induction of autoimmune abdominal aortic aneurysm in pigs : A novel large animal model. / Riber, Sara Schødt; Ali, Mulham; Bergseth, Sara Hveding; Stubbe, Jane; Stenger, Michael; Behr-Rasmussen, Carsten; Lindholt, Jes Sanddal.

I: Annals of Medicine and Surgery, Bind 20, 08.2017, s. 26-31.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Induction of autoimmune abdominal aortic aneurysm in pigs

T2 - A novel large animal model

AU - Riber, Sara Schødt

AU - Ali, Mulham

AU - Bergseth, Sara Hveding

AU - Stubbe, Jane

AU - Stenger, Michael

AU - Behr-Rasmussen, Carsten

AU - Lindholt, Jes Sanddal

PY - 2017/8

Y1 - 2017/8

N2 - Background 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. Methods 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. Results 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. Conclusion 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.

AB - Background 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. Methods 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. Results 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. Conclusion 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.

KW - Abdominal aortic aneurysm

KW - Autoimmunity

KW - Porcine model

KW - Sheep-to-pig xenotransplantation

U2 - 10.1016/j.amsu.2017.06.017

DO - 10.1016/j.amsu.2017.06.017

M3 - Journal article

C2 - 28702183

AN - SCOPUS:85021224173

VL - 20

SP - 26

EP - 31

JO - Annals of Medicine and Surgery

JF - Annals of Medicine and Surgery

SN - 2049-0801

ER -