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Abstract: P249 LOSS OF ENDOTHELIAL INTEGRITY AND ENDOTHELIAL ACTIVATION PRECEDE INTIMAL HYPERPLASIA IN SURGICALLY TRANSFERRED VENOUS GRAFTS IN MICE
Poster - BASIC SCIENCE - Other Vascular Cells Abstract: P249 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
LOSS OF ENDOTHELIAL INTEGRITY AND ENDOTHELIAL ACTIVATION PRECEDE INTIMAL HYPERPLASIA IN SURGICALLY TRANSFERRED VENOUS GRAFTS IN MICE C-N Tseng, E Karlöf, U Hedin, E Eriksson Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm Objectives–Peripheral veins are used in vascular grafting. However, venous grafts (VGs) degenerate after implantation in the arterial circulation. Intimal hyperplasia (IH) in VGs is critical in VG disease. The mechanisms that mediate IH are unclear. Methods–VG implantation was performed by end-to-end anastomosis of the thoracic vena cava from donor mice to the abdominal aorta in recipients. Histology, immunohistochemistry (IHC) and scanning electron microscopy (SEM) were used to study endothelium (EC) and the development of IH. Intravital microscopy (IVM) was used to study interactions between leukocytes and EC. Results–VGs were studied at different time points postoperatively (Time 0, 3, 4, 7, 28, 63 days). We found that graft EC suffers injury that is most pronounced by 7 days. ECs are fully regenerated by 28 days, but the surface remains irregular. No EC injury was seen in surgically transferred aortas or in VGs immediately after surgery, indicating a role for arterial hemodynamics acting on VGs in the loss of EC integrity. IVM showed slow rolling of leukocytes along EC in grafts whereas no rolling was observed in the aorta. Rolling was also observed in the native IVC, however at higher velocity than in VGs indicating EC activation in the graft. IH developed in VGs by 28 days. Conclusions–We demonstrate EC damage and activation in response to venous grafting in a mouse model. Further studies will aim at determining the roles for EC injury and inflammation in the loss of VG patency. Funding: This work was supported by the Swedish Heart-Lung Foundation, the Swedish Research Council, and Karolinska Institutet.
LOSS OF ENDOTHELIAL INTEGRITY AND ENDOTHELIAL ACTIVATION PRECEDE INTIMAL HYPERPLASIA IN SURGICALLY TRANSFERRED VENOUS GRAFTS IN MICE C-N Tseng, E Karlöf, U Hedin, E Eriksson Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm Objectives–Peripheral veins are used in vascular grafting. However, venous grafts (VGs) degenerate after implantation in the arterial circulation. Intimal hyperplasia (IH) in VGs is critical in VG disease. The mechanisms that mediate IH are unclear. Methods–VG implantation was performed by end-to-end anastomosis of the thoracic vena cava from donor mice to the abdominal aorta in recipients. Histology, immunohistochemistry (IHC) and scanning electron microscopy (SEM) were used to study endothelium (EC) and the development of IH. Intravital microscopy (IVM) was used to study interactions between leukocytes and EC. Results–VGs were studied at different time points postoperatively (Time 0, 3, 4, 7, 28, 63 days). We found that graft EC suffers injury that is most pronounced by 7 days. ECs are fully regenerated by 28 days, but the surface remains irregular. No EC injury was seen in surgically transferred aortas or in VGs immediately after surgery, indicating a role for arterial hemodynamics acting on VGs in the loss of EC integrity. IVM showed slow rolling of leukocytes along EC in grafts whereas no rolling was observed in the aorta. Rolling was also observed in the native IVC, however at higher velocity than in VGs indicating EC activation in the graft. IH developed in VGs by 28 days. Conclusions–We demonstrate EC damage and activation in response to venous grafting in a mouse model. Further studies will aim at determining the roles for EC injury and inflammation in the loss of VG patency. Funding: This work was supported by the Swedish Heart-Lung Foundation, the Swedish Research Council, and Karolinska Institutet.