Fetuin-A expression in early venous stenosis formation in a porcine model of hemodialysis graft failure.
OBJECTIVE
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.


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 alpha-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.
Misra
Sanjay
S
Department of Radiology, Mayo Clinic College of Medicine, 200 First Street Southwest, Alfred 6460, Rochester, MN 55905, USA. misra.sanjay@mayo.edu
Fu
Alex A
AA
Anderson
Jill L
JL
Glockner
James F
JF
McKusick
Michael A
MA
Bjarnason
Haraldur
H
Woodrum
David A
DA
Mukhopadhyay
Debabrata
D
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D006083:Graft Occlusion, Vascular / Q000378:metabolism*; D008297:Male; D013552:Swine; D014689:Venous Insufficiency / Q000378:metabolism*; D060749:alpha-2-HS-Glycoprotein
D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein