The Rat Femoral Arteriovenous Fistula Model: Increased Expression of Matrix Metalloproteinase–2 and −9 at the Venous Stenosis

Misra, Sanjay; Fu, Alex A.; Anderson, J. L.; Sethi, Sanjeev; Glockner, James F.; McKusick, Michael A.; Bjarnason, Haraldur; Woodrum, David A.; Mukhopadhyay, Debabrata

doi:10.1016/j.jvir.2008.01.005

Cited by 50 publications

(65 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because certain MMPs can increase the bioavailability of VEGF-A, potentially accelerating the formation of venous stenotis, we examined the expression of MMPs and their inhibitiors in the venous stenosis (6,30,35,36,38,49). In our previous study in a porcine model, MMP-2 activity peaked at the vein-to-graft anastomosis by day 7 (35).…”

Section: Discussionmentioning

confidence: 99%

“…The proteins of interest exhibit a high degree of homology between pigs and human; these antibodies have been used in pigs as previously described (4,23,28,43). Zymography was performed on whole tissue lysate as previously described (35)(36)(37).…”

Section: Methodsmentioning

confidence: 99%

“…Another group of cytokines that are thought to play a key role in hemodialysis graft failure and remodeling of vein grafts used as arterial conduits are matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs) (6,35,36,38,49). This contention is based on the observations that an imbalance of MMP activity over TIMPs promotes the migration and proliferation of smooth muscle cells (2,21) and that certain MMPs increase the bioavailability of VEGF-A, potentially accelerating the development of intimal hyperplasia (30).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts

Misra¹,

Fu²,

Puggioni³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

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 α-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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts

Misra¹,

Fu²,

Puggioni³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The main advantages of small animal models are that they allow for evaluation of specific pathways through specific knockout genes. The main small-animal models of dialysis access have been murine and rodents model (26,32,39,62,63). Large-animal models are advantageous because they have vessel anatomy similar to that of humans and provide the opportunity to study in detail hemodynamics and histology, but also allow for testing of experimental drug therapies and devices.…”

Section: Future Perspectives: New Frontiers In Vascular Access Researmentioning

confidence: 99%

Novel Paradigms for Dialysis Vascular Access

Lee

2013

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

SummaryVascular access dysfunction is a major cause of morbidity and mortality in hemodialysis patients. The most common cause of vascular access dysfunction is venous stenosis from neointimal hyperplasia within the perianastomotic region of an arteriovenous fistula and at the graft-vein anastomosis of an arteriovenous graft. There have been few, if any, effective treatments for vascular access dysfunction because of the limited understanding of the pathophysiology of venous neointimal hyperplasia formation. This review will (1) describe the histopathologic features of hemodialysis access stenosis; (2) discuss novel concepts in the pathogenesis of neointimal hyperplasia development, focusing on downstream vascular biology; (3) highlight future novel therapies for treating downstream biology; and (4) discuss future research areas to improve our understanding of downstream biology and neointimal hyperplasia development.

show abstract

“…In order to advance the field further, we need to further our current understanding of both the clinical and experimental pathways that result in venous neointimal hyperplasia and mechanisms that lead to biofilm and fibrin sheath production in C V C s b y u s i n g t h e a d v a n c e d technologies and tools in cellular and molecular biology, bioengineering, genomics, proteomics, and vascular imaging (ultrasound, computed tomography, and magnetic resonance imaging) 65,124,214 . Finally, small and large animal models of AVF and AVG, which a number of investigators in this field have already developed 61,93,207,[215][216][217] , will play an essential role in "translating" our knowledge of pathophysiologic mechanisms in vascular access dysfunction to novel therapies for patients.…”

Section: Future Perspectives: New Frontiers In Researchmentioning

confidence: 99%

Hemodialysis Vascular Access Dysfunction

Lee¹

2011

Progress in Hemodialysis - From Emergent Biotechnology to Clinical Practice

View full text Add to dashboard Cite

The Rat Femoral Arteriovenous Fistula Model: Increased Expression of Matrix Metalloproteinase–2 and −9 at the Venous Stenosis

Cited by 50 publications

References 23 publications

Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts

Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts

Novel Paradigms for Dialysis Vascular Access

Hemodialysis Vascular Access Dysfunction

Contact Info

Product

Resources

About