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MORPHOLOGIC REACTION PATTERNS TO AORTIC STENT GRAFT INCORPORATION
Cardiovascular Pathology 13 (2004) S17 – S79
Poster Abstracts–Wednesday June 2, 2004 Aneurysms
P002
P001
CHARACTERIZATION OF ANEURYSMS IN A HYPOMORPHIC PKD1-MOUSE MODEL. Sabrin Hassane, Irma S. Lantinga-van Leeuwen, J. Conny Van Munsteren, Wouter Leonhard, Nanna Claij, Martijn H. Breuning, Adriana C. Gittenberger-de Groot, Dorien J.M. Peters, Marco C. DeRuiter. Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands, Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
MORPHOLOGIC REACTION PATTERNS TO AORTIC STENT GRAFT INCORPORATION. Elisabeth Harrer, Peter Grewe, Thorben Ick, Klaus-Michael Mu¨ller. Institute of Pathology, University Hospital Bergmannsheil, Ruhr-University, Bochum, Germany, Department of Cardiology, University Hospital Bergmannsheil, Ruhr-University, Bochum, Germany. Aims: Over the past decade endovascular aortic stent grafts have become a useful alternative to open surgery for a selected group of patients. However, there is still little information available regarding histomorphological correlates of clinically evident incorporation behaviour and complications. The aim was to identify and characterize morphological incorporation patterns of aortic stent grafts particularly with a view to complications. Materials and Methods: 5 surgically resected and 4 autoptic aortic stent grafts of commonly implanted devices were examined. The stent grafts had remained in-situ between 6 months to 6 years. Following macroscopic and radiographic evaluation, the specimens were cut into segments using a special cutting device. Sections were then prepared for histomorphologic, immunohistochemical and electron microscopic analysis. Findings were compared with ultrasonographic and computertomographic images as well as with animal models. Results: The topographic variability of underlying atherosclerotic plaques determined stent graft incorporation. Deformed aortic wall segments induced a variety of structural changes including lacerations of the coat. Stent graft anchorage particularly at the proximal and distal neck of the aneurysm was inadequate in areas with combined and hard plaques. Transprosthetic incorporation was also incomplete or even absent in regions overlying advanced atherosclerotic lesions (Stary type IV to VI). As a consequence endoleaks developed preventing thrombosis of the space between aneurysmal walls and the outside the stent graft to occur. This in turn propagated stent graft dislocation. Thromboses and intimal hyperplasia were pronounced in particularly distorted regions. Atherosclerotic changes in the neointimal layer showed no relationship with underlying atherosclerotic changes in the native artery. The development of neointimal atherosclerotic changes ran a course independent of stent graft anchorage and transprosthetic incorporation. Inflammatory infiltrates and neovascularisation were particularly evident in areas adjacent to stent struts. Ultrasound and computertomographic images could only display a crude picture of the incoporation patterns of stent grafts. Early morphological correlates of clinical complications could thus not be identified. Compared with humans, animal models reflected the morphology of stent graft incorporation patterns only to a limited extent. Conclusion: The findings presented illustrate the dynamics of aortic stent graft incorporation patterns and resulting complications. Aortic stent grafts display individually highly variable reaction patterns. These are most of all governed by the state of the diseased native artery.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multisystem disorder characterized by bilateral progressive cysts formation in kidneys. Serious complications of this disease are intracranial and aortic aneurysms. The incidence of aneurysms in ADPKD-patients is approximately 10% compared to 1% in the general population. The condition is mainly caused by mutations in the PKD1 or PKD2 gene, encoding the proteins polycystin-1 and polycystin-2, respectively. These proteins seem to be involved in cellular signalling, cell adhesion and mechanosensation and can interact with each other. In blood vessels polycystin-1 and -2 are expressed in vascular smooth muscle cells (SMC) and endothelial cells (EC). We have generated a hypomorphic Pkd1-mouse model with a considerable reduction of the normal Pkd1 transcript, in which dissecting aneurysms in the thoracic and abdominal aorta occur. Using (immuno)histochemistry we have characterized changes in the extracellular matrix composition and the phenotype of the SMC and EC in the dissecting aneurysms of the aorta of four-week-old homozygous mice. Overall the aorta shows regions with increased cell numbers between elastin fibres. Also disarrangement and abnormal morphology of SMC were detected. This coincides with loss of a-smooth-muscle-actin in SMC and up-regulation of proteoglycans, which may indicate a switch in SMC phenotype from contractile to a more synthetic phenotype. At the regions where the dissection begins, cystic medial necrosis was observed with detachment of EC from the elastic lamina interna, ruptured elastin fibres and reduction in SMC in the tunica media. In the adjacent regions large mural bleedings were seen. In conclusion, in our mouse model reduced levels of polycystin-1 during maturation of the vessel wall, resulted in aneurysms with changes in extracellular matrix composition and changes in smooth muscle cell phenotypes similar to human aneurysms.
P003 INFLUENCE OF INTRALUMINAL THROMBUS ON STRUCTURAL FEATURES AND GENE EXPRESSION OF THE ANEURYSM WALL. Monsur Kazi1,2, Joy Roy2,3, Hanna Bjo¨rk1, Chaoyong Zhu1, Anders Hamsten1, Jesper Swedenborg2, Ulf Hedin2, Per Eriksson1. 1King Gustav V Research Institute, Karolinska Hospital, Karolinska institutet, Stockholm, Sweden, 2Department of Vascular Surgery, Karolinska Hospital, Karolinska institutet, Stockholm, Sweden, 3St Go¨ran Hospital, Stockholm, Sweden. Introduction: It has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAA) affects the underlying vessel wall. Aneurysm enlargement has been associated with growth of the thrombus
1054-8807/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2004.03.043
Poster Abstracts–Wednesday June 2, 2004 Aneurysms
P002
P001
CHARACTERIZATION OF ANEURYSMS IN A HYPOMORPHIC PKD1-MOUSE MODEL. Sabrin Hassane, Irma S. Lantinga-van Leeuwen, J. Conny Van Munsteren, Wouter Leonhard, Nanna Claij, Martijn H. Breuning, Adriana C. Gittenberger-de Groot, Dorien J.M. Peters, Marco C. DeRuiter. Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands, Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
MORPHOLOGIC REACTION PATTERNS TO AORTIC STENT GRAFT INCORPORATION. Elisabeth Harrer, Peter Grewe, Thorben Ick, Klaus-Michael Mu¨ller. Institute of Pathology, University Hospital Bergmannsheil, Ruhr-University, Bochum, Germany, Department of Cardiology, University Hospital Bergmannsheil, Ruhr-University, Bochum, Germany. Aims: Over the past decade endovascular aortic stent grafts have become a useful alternative to open surgery for a selected group of patients. However, there is still little information available regarding histomorphological correlates of clinically evident incorporation behaviour and complications. The aim was to identify and characterize morphological incorporation patterns of aortic stent grafts particularly with a view to complications. Materials and Methods: 5 surgically resected and 4 autoptic aortic stent grafts of commonly implanted devices were examined. The stent grafts had remained in-situ between 6 months to 6 years. Following macroscopic and radiographic evaluation, the specimens were cut into segments using a special cutting device. Sections were then prepared for histomorphologic, immunohistochemical and electron microscopic analysis. Findings were compared with ultrasonographic and computertomographic images as well as with animal models. Results: The topographic variability of underlying atherosclerotic plaques determined stent graft incorporation. Deformed aortic wall segments induced a variety of structural changes including lacerations of the coat. Stent graft anchorage particularly at the proximal and distal neck of the aneurysm was inadequate in areas with combined and hard plaques. Transprosthetic incorporation was also incomplete or even absent in regions overlying advanced atherosclerotic lesions (Stary type IV to VI). As a consequence endoleaks developed preventing thrombosis of the space between aneurysmal walls and the outside the stent graft to occur. This in turn propagated stent graft dislocation. Thromboses and intimal hyperplasia were pronounced in particularly distorted regions. Atherosclerotic changes in the neointimal layer showed no relationship with underlying atherosclerotic changes in the native artery. The development of neointimal atherosclerotic changes ran a course independent of stent graft anchorage and transprosthetic incorporation. Inflammatory infiltrates and neovascularisation were particularly evident in areas adjacent to stent struts. Ultrasound and computertomographic images could only display a crude picture of the incoporation patterns of stent grafts. Early morphological correlates of clinical complications could thus not be identified. Compared with humans, animal models reflected the morphology of stent graft incorporation patterns only to a limited extent. Conclusion: The findings presented illustrate the dynamics of aortic stent graft incorporation patterns and resulting complications. Aortic stent grafts display individually highly variable reaction patterns. These are most of all governed by the state of the diseased native artery.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multisystem disorder characterized by bilateral progressive cysts formation in kidneys. Serious complications of this disease are intracranial and aortic aneurysms. The incidence of aneurysms in ADPKD-patients is approximately 10% compared to 1% in the general population. The condition is mainly caused by mutations in the PKD1 or PKD2 gene, encoding the proteins polycystin-1 and polycystin-2, respectively. These proteins seem to be involved in cellular signalling, cell adhesion and mechanosensation and can interact with each other. In blood vessels polycystin-1 and -2 are expressed in vascular smooth muscle cells (SMC) and endothelial cells (EC). We have generated a hypomorphic Pkd1-mouse model with a considerable reduction of the normal Pkd1 transcript, in which dissecting aneurysms in the thoracic and abdominal aorta occur. Using (immuno)histochemistry we have characterized changes in the extracellular matrix composition and the phenotype of the SMC and EC in the dissecting aneurysms of the aorta of four-week-old homozygous mice. Overall the aorta shows regions with increased cell numbers between elastin fibres. Also disarrangement and abnormal morphology of SMC were detected. This coincides with loss of a-smooth-muscle-actin in SMC and up-regulation of proteoglycans, which may indicate a switch in SMC phenotype from contractile to a more synthetic phenotype. At the regions where the dissection begins, cystic medial necrosis was observed with detachment of EC from the elastic lamina interna, ruptured elastin fibres and reduction in SMC in the tunica media. In the adjacent regions large mural bleedings were seen. In conclusion, in our mouse model reduced levels of polycystin-1 during maturation of the vessel wall, resulted in aneurysms with changes in extracellular matrix composition and changes in smooth muscle cell phenotypes similar to human aneurysms.
P003 INFLUENCE OF INTRALUMINAL THROMBUS ON STRUCTURAL FEATURES AND GENE EXPRESSION OF THE ANEURYSM WALL. Monsur Kazi1,2, Joy Roy2,3, Hanna Bjo¨rk1, Chaoyong Zhu1, Anders Hamsten1, Jesper Swedenborg2, Ulf Hedin2, Per Eriksson1. 1King Gustav V Research Institute, Karolinska Hospital, Karolinska institutet, Stockholm, Sweden, 2Department of Vascular Surgery, Karolinska Hospital, Karolinska institutet, Stockholm, Sweden, 3St Go¨ran Hospital, Stockholm, Sweden. Introduction: It has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAA) affects the underlying vessel wall. Aneurysm enlargement has been associated with growth of the thrombus
1054-8807/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2004.03.043