TY - JOUR
T1 - Fetuin-A Expression in Early Venous Stenosis Formation in a Porcine Model of Hemodialysis Graft Failure
AU - Misra, Sanjay
AU - Fu, Alex A.
AU - Anderson, Jill L.
AU - Glockner, James F.
AU - McKusick, Michael A.
AU - Bjarnason, Haraldur
AU - Woodrum, David A.
AU - Mukhopadhyay, Debabrata
N1 - Funding Information:
This work was supported by National Institutes of Health grants CA78383, HL072178, and HL70567; and a grant from the American Cancer Society to D.M. None of the authors have identified a conflict of interest.
PY - 2008/10
Y1 - 2008/10
N2 - Purpose: Because fetuin-A is a cytokine with multifunctional effects on vascular smooth muscle cells and fibroblasts, the authors examined the course of its expression in early venous stenosis formation in a porcine model of chronic renal insufficiency with polytetrafluoroethylene (PTFE) arteriovenous (AV) hemodialysis grafts. Materials and Methods: Pigs had chronic renal insufficiency created by complete embolization of the left kidney and partial embolization of the right kidney. Twenty-eight days later, PTFE AV grafts were placed from the carotid artery to the ipsilateral jugular vein, and the animals were euthanized 3 days (n = 4), 7 days (n = 4), or 14 days (n = 4) later. Expression of fetuin-A was determined by Western blot analysis of the venous stenosis, control veins, and plasma. Immunohistochemical analysis of the venous stenosis and control vein was performed. Blood urea nitrogen (BUN) and creatinine were measured before embolization and at the time of graft placement. Results: The mean BUN and creatinine levels at graft placement were significantly higher than before embolization (P < .05). Severe venous neointimal hyperplasia occurred by day 14 and was characterized by primarily α-smooth muscle actin-positive cells. By day 14, fetuin-A levels had increased significantly (P < .05) at the venous stenosis compared with control veins and in the serum compared with measurements before embolization. Conclusions: Significantly increased expression of fetuin-A was observed in early venous stenosis by day 14 and in serum compared with baseline measurements. Understanding the role of fetuin-A in venous neointimal hyperplasia could help in improving outcomes in patients undergoing hemodialysis.
AB - Purpose: Because fetuin-A is a cytokine with multifunctional effects on vascular smooth muscle cells and fibroblasts, the authors examined the course of its expression in early venous stenosis formation in a porcine model of chronic renal insufficiency with polytetrafluoroethylene (PTFE) arteriovenous (AV) hemodialysis grafts. Materials and Methods: Pigs had chronic renal insufficiency created by complete embolization of the left kidney and partial embolization of the right kidney. Twenty-eight days later, PTFE AV grafts were placed from the carotid artery to the ipsilateral jugular vein, and the animals were euthanized 3 days (n = 4), 7 days (n = 4), or 14 days (n = 4) later. Expression of fetuin-A was determined by Western blot analysis of the venous stenosis, control veins, and plasma. Immunohistochemical analysis of the venous stenosis and control vein was performed. Blood urea nitrogen (BUN) and creatinine were measured before embolization and at the time of graft placement. Results: The mean BUN and creatinine levels at graft placement were significantly higher than before embolization (P < .05). Severe venous neointimal hyperplasia occurred by day 14 and was characterized by primarily α-smooth muscle actin-positive cells. By day 14, fetuin-A levels had increased significantly (P < .05) at the venous stenosis compared with control veins and in the serum compared with measurements before embolization. Conclusions: Significantly increased expression of fetuin-A was observed in early venous stenosis by day 14 and in serum compared with baseline measurements. Understanding the role of fetuin-A in venous neointimal hyperplasia could help in improving outcomes in patients undergoing hemodialysis.
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U2 - 10.1016/j.jvir.2008.06.007
DO - 10.1016/j.jvir.2008.06.007
M3 - Article
C2 - 18693047
AN - SCOPUS:52149122268
SN - 1051-0443
VL - 19
SP - 1477
EP - 1482
JO - Journal of Vascular and Interventional Radiology
JF - Journal of Vascular and Interventional Radiology
IS - 10
ER -