Venous stenosis in a pig arteriovenous fistula model--anatomy, mechanisms and cellular phenotypes

Wang, Yang; Krishnamoorthy, Mahesh; Banerjee, Rupak K.; Zhang, Jianhua; Rudich, Steven; Holland, Christy K.; Arend, Lois J.; Roy‐Chaudhury, Prabir

doi:10.1093/ndt/gfm547

Cited by 101 publications

(121 citation statements)

References 37 publications

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“…These results were corroborated by Cheung and colleagues, who showed in a porcine AVG model that adventitial fibroblasts begin to differentiate into myofibroblasts and contribute to neointimal cells (43). Roy-Chaudhury and colleagues have also demonstrated that myofibroblasts contribute to venous stenosis formation in a porcine AVF model (44).…”

Section: Origins Of Neointimal Cells In Vascular Access Dysfunctionmentioning

confidence: 59%

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

Lee

Misra

2016

CJASN

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Vascular access dysfunction remains a major cause of morbidity and mortality in hemodialysis patients. At present there are few effective therapies for this clinical problem. The poor understanding of the pathobiology that leads to arteriovenous fistula (AVF) and graft (AVG) dysfunction remains a critical barrier to development of novel and effective therapies. However, in recent years we have made substantial progress in our understanding of the mechanisms of vascular access dysfunction. This article presents recent advances and new insights into the pathobiology of AVF and AVG dysfunction and highlights potential therapeutic targets to improve vascular access outcomes.

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Section: Origins Of Neointimal Cells In Vascular Access Dysfunctionmentioning

confidence: 59%

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

Lee

Misra

2016

CJASN

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“…Intimal hyperplasia is produced by the proliferation of vascular smooth muscle cells together with matrix deposition (31,47,51,59). While various cytokines have been implicated in this process, one that may be of particular importance is VEGF, specifically VEGF-A.…”

mentioning

confidence: 99%

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

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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.

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“…The pathogenesis in AVFs that fail to mature (early failure) for dialysis, in contrast to AVG and late AVF failure, remains poorly understood. At a histological level early AVF failure is also characterized by aggressive neointimal hyperplasia in both animal and human models, seen as early as 1 month in animals 63,71 and 3 months in humans 64,66 . The underlying factors (upstream events) which may contribute to early AVF failure, include 4,[72][73][74][75][76][77][78][79][80][81] : (1) small diameter sizes in the vein and artery, (2) surgical injury at the time AV fistula placement, (3) previous venipunctures, (4) development of accessory veins after surgery, (5) hemodynamic shear stress at the AV anastomosis, (6) a genetic predisposition to vascular constriction and neointimal hyperplasia, and (7) pre-existing venous neointimal hyperplasia.…”

Section: Pathophysiologic Mechanisms Of Neointimal Hyperplasia Formatmentioning

confidence: 99%

Hemodialysis Vascular Access Dysfunction

Lee¹

2011

Progress in Hemodialysis - From Emergent Biotechnology to Clinical Practice

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Venous stenosis in a pig arteriovenous fistula model--anatomy, mechanisms and cellular phenotypes

Cited by 101 publications

References 37 publications

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes

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

Hemodialysis Vascular Access Dysfunction

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