Remodeling of experimental arteriovenous fistula with increased matrix metalloproteinase expression in rats

Chan, Chih-Yang; Chen, Yih‐Sharng; Ma, Ming‐Chieh; Chen, Chou-Fong

doi:10.1016/j.jvs.2006.12.063

Cited by 57 publications

(75 citation statements)

References 34 publications

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“…Immunohistochemistry showed that expression of α-SMA in the experimental group gradually increased with time. The α-SMA-positive area of the tunica intima and tunica media in the vein near the anastomotic stoma of the experimental group increased significantly compared with that in the sham operation surgery group at the same time-point in weeks 1 and 4, indicating that the expression of α-SMA may increase with increased intimal hyperplasia, consistent with previous studies (7,(29)(30)(31).…”

Section: Daysupporting

confidence: 90%

“…However, large animals have high feeding costs and a complex process of anesthesia, and it can be difficult to establish a mixed model of disease, such as with diabetes or chronic renal failure. Small animal models do not have these deficiencies (6)(7)(8)(9), and the wide use of gene knockout rats in recent years is particularly important, as it provides an important platform for the study of the mechanisms of the occurrence and development of diseases. The establishment of an arteriovenous fistula model in animals with chronic renal failure by a cuff technique has been reported (10), but the experimental results are often influenced by the technology proficiency level of the practitioner.…”

Section: Introductionmentioning

confidence: 99%

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Establishment of a rat autogenous arteriovenous fistula model following 5/6 nephrectomy

Cheng

Zhou

Huang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of this study was to establish a stable rat model of autogenous arteriovenous fistula (AVF) with chronic renal function insufficiency. Forty Sprague-Dawley rats were randomly divided into an experimental group (n=20) and sham surgery group (n=20) and a 5/6 nephrectomy model was established in the rats. One week later, in the experimental group, the ipsilateral caroid artery was inserted into the external jugular vein by a cuff technique to establish a carotid arteriovenous fistula; in the sham group, the external jugular vein and carotid artery were dissociated. At 7 and 28 days following the establishment of the AVF, the renal functions of the two groups were measured. Hematoxylin and eosin staining and double collagen and elastin staining were conducted to evaluate the area of intimal hyperplasia in the external jugular vein, and the expression of α-smooth muscle actin in the vein was investigated by immunohistochemistry. The creatinine and urea nitrogen levels in the experimental group at each time-point were significantly higher than those in the sham surgery group (P<0.05). The intimal hyperplasia of the external jugular vein of the experimental group was increased significantly compared with that in the sham group at each time-point (P<0.05). The model, which is easy to establish and simple to master, provides a new and feasible experimental method for the study of intimal hyperplasia associated with autogenous AVF in chronic renal insufficiency, and is worthy of wider use.

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Section: Daysupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Establishment of a rat autogenous arteriovenous fistula model following 5/6 nephrectomy

Cheng

Zhou

Huang

et al. 2015

Experimental and Therapeutic Medicine

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“…First, the low-resistance circuit resulting from creation of the AV anastomosis triggers an immediate increase in blood flow and wall shear stress (WSS) through the inflow artery (5)(6)(7). Second, these rapid increases in arterial blood flow and WSS stimulate an endothelium-dependent vasodilatory response in the artery and vein, mediated largely by nitric oxide (NO) and activation of matrix metalloproteinases (MMPs), that dilates both the inflow artery and outflow vein, restores WSS toward baseline, and inhibits neointimal hyperplasia development (7)(8)(9)(10)(11). Appropriate upregulation of MMPs results in matrix degradation and restructuring of the vascular scaffold, leading to luminal expansion (9,11,12).…”

Section: Vascular Remodeling and Neointimal Hyperplasia Developmentmentioning

confidence: 99%

“…Second, these rapid increases in arterial blood flow and WSS stimulate an endothelium-dependent vasodilatory response in the artery and vein, mediated largely by nitric oxide (NO) and activation of matrix metalloproteinases (MMPs), that dilates both the inflow artery and outflow vein, restores WSS toward baseline, and inhibits neointimal hyperplasia development (7)(8)(9)(10)(11). Appropriate upregulation of MMPs results in matrix degradation and restructuring of the vascular scaffold, leading to luminal expansion (9,11,12). Finally, successful vascular remodeling restores WSS toward normal levels in a vessel with increased blood flow and helps maintain luminal diameter (6,13), a key hallmark of successful outward AVF remodeling.…”

Section: Vascular Remodeling and Neointimal Hyperplasia Developmentmentioning

confidence: 99%

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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“…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%

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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Remodeling of experimental arteriovenous fistula with increased matrix metalloproteinase expression in rats

Abstract: The present results confirmed our hypothesis that a high blood flow rate in the fistula vein affects the expression of MMPs and TIMP-4, resulting in the remodeling or maturation of the AVF. Remodeling is associated with degradation of collagen, with an increase in the collagen I/III ratio.

Cited by 57 publications

References 34 publications

Establishment of a rat autogenous arteriovenous fistula model following 5/6 nephrectomy

Establishment of a rat autogenous arteriovenous fistula model following 5/6 nephrectomy

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

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