| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Radiology, 2Division of Vascular Surgery, 3Division of Biostatistics, 4Division of Hypertension and Nephrology, 5University of Minnesota Medical School, 6Mayo Medical School, and 7Department of Biochemistry and Molecular Biology, Minneapolis; and Mayo Clinic College of Medicine, Rochester, Minnesota
Submitted 5 June 2007 ; accepted in final form 28 February 2008
Venous injury and subsequent venous stenosis formation are responsible for hemodialysis graft failure. Our hypothesis is that these pathological changes are in part related to changes in wall shear stress (WSS) that results in the activation of matrix regulatory proteins causing subsequent venous stenosis formation. In the present study, we examined the serial changes in WSS, blood flow, and luminal vessel area that occur subsequent to the placement of a hemodialysis graft in a porcine model of chronic renal insufficiency. We then determined the corresponding histological, morphometric, and kinetic changes of several matrix regulatory proteins including VEGF-A, its receptors, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and TIMP-2. WSS was estimated by obtaining blood flow and luminal vessel area by performing phase-contrast MRI with magnetic resonance angiography in 21 animals at 1 day after graft placement and prior to death on day 3 (n = 7), day 7 (n = 7), and day 14 (n = 7). At all time points, the mean WSS at the vein-to-graft anastomosis was significantly higher than that at the control vein (P < 0.05). WSS had a bimodal distribution with peaks on days 1 and 7 followed by a significant reduction in WSS by day 14 (P < 0.05 compared with day 7) and a decrease in luminal vessel area compared with control vessels. By day 3, there was a significant increase in VEGF-A and pro-MMP-9 followed by, on day 7, increased pro-MMP-2, active MMP-2, and VEGF receptor (VEGFR)-2 (P < 0.05) and, by day 14, increased VEGFR-1 and TIMP-1 (P < 0.05) at the vein-to-graft anastomosis compared with control vessels. Over time, the neointima thickened and was composed primarily of 
-smooth muscle actin-positive cells with increased cellular proliferation. Our data suggest that hemodialysis graft placement leads to early increases in WSS, VEGF-A, and pro-MMP-9 followed by subsequent increases in pro-MMP-2, active MMP-2, VEGFR-1, VEGFR-2, and TIMP-1, which may contribute to the development of venous stenosis.
wall shear stress; matrix metalloproteinases; vascular endothelial growth factor-A; hemodialysis grafts; vascular biology; tissue inhibitors of matrix metalloproteinase
This article has been cited by other articles:
|
|
 |
|
  Z.-D. Shi, X.-Y. Ji, H. Qazi, and J. M. Tarbell Interstitial flow promotes vascular fibroblast, myofibroblast, and smooth muscle cell motility in 3-D collagen I via upregulation of MMP-1 Am J Physiol Heart Circ Physiol, October 1, 2009; 297(4): H1225 - H1234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Misra, A. A. Fu, K. D. Misra, J. F. Glockner, and D. Mukhopadhyay Wall Shear Stress Measurement Using Phase Contrast Magnetic Resonance Imaging With Phase Contrast Magnetic Resonance Angiography in Arteriovenous Polytetrafluoroethylene Grafts Angiology, August 1, 2009; 60(4): 441 - 447. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Hughes, A. A. Fu, A. Puggioni, J. F. Glockner, B. Anwer, A. M. McGuire, D. Mukhopadhyay, and S. Misra Adventitial transplantation of blood outgrowth endothelial cells in porcine haemodialysis grafts alleviates hypoxia and decreases neointimal proliferation through a matrix metalloproteinase-9-mediated pathway--a pilot study Nephrol. Dial. Transplant., January 1, 2009; 24(1): 85 - 96. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
