Increased Expression of HIF-1α, VEGF-A and Its Receptors, MMP-2, TIMP-1, and ADAMTS-1 at the Venous Stenosis of Arteriovenous Fistula in a Mouse Model with Renal Insufficiency

Misra, Sanjay; Shergill, Uday; Yang, Binxia; Janardhanan, Rajiv; Misra, Khamal D.

doi:10.1016/j.jvir.2010.02.043

Cited by 64 publications

(120 citation statements)

References 31 publications

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“…Chronic renal insufficiency was created by performing a nephrectomy of the right kidney combined with ligation of the upper polar branch of the renal artery to the left kidney [5]. In this model, after this procedure, the average BUN and creatinine are significantly elevated twenty-eight days later [5]. Four weeks later, a carotid artery to jugular vein AVF was created (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Four weeks later, a carotid artery to jugular vein AVF was created (Fig. 1) [5, 6]. The shRNA for Vegf-A was purchased from Open Biosystems (Huntsville, AL) and it was prepared according to the manufacturer's protocol [7].…”

Section: Methodsmentioning

confidence: 99%

“…Fourteen days later, the same therapy was repeated using a separate surgical procedure [8]. Previously, experiments conducted using this technique have shown that venous stenosis forms in this model at the outflow vein [5–7, 9–11]. Seventy-nine male C57BL/6 mice weighing 25–30 grams underwent nephrectomy.…”

Section: Methodsmentioning

confidence: 99%

“…The vessels were homogenized and the RNA was isolated using RNeasy mini kit (Qiagen) [5, 6]. The gene expression of interest was determined using RT-PCR analysis [6].…”

Section: Methodsmentioning

confidence: 99%

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The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

Janardhanan¹,

Yang²,

Kilari³

et al. 2016

Journal of Vascular and Interventional Radiology

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Purpose Previous study has demonstrated that adventitial delivery of lentivirus mediated Vegf-A shRNA (LV-shRNA-Vegf-A, small hairpin RNA that inhibits Vegf-A gene expression) at the time of arteriovenous fistula (AVF) creation increases the lumen vessel area (LVA) of the outflow vein and reduces venous neointimal hyperplasia (VNH). However, the effect of decreasing Vegf-A and improving LVA decreases by 2-weeks as stenosis develops. The aim of the present study was to determine if a second dose of LV-shRNA-Vegf-A could improve LVA and decrease VNH. Methods Chronic kidney disease was created in C57BL/6 mice and 28 days later, a AVF was created by connecting right carotid artery to ipsilateral jugular vein. 5×106 plaque forming units of LV-shRNA-Vegf-A or control shRNA was administered to the adventitia of the outflow vein immediately after AVF creation and a second dose of the same treatment fourteen days later. Animals were sacrificed at 21, 28, and 42 days after AVF creation for reverse transcription polymerase chain reaction (RT-PCR) and histomorphometric analyses. Results By day 21, there was a 25% increase in the average LVA (day 21: P=0.11), with a decrease in cell proliferation (day 21: P=0.0079, day 28: P=0.28; day 42: P=0.5), decrease in α-smooth muscle cell actin staining (day 21: P<0.0001, day 28: P<0.05; day 42: P=0.59), and decrease in hypoxic stress (day 21: P<0.001, day 28: P=0.28; day 42: P=0.46) in LV versus control shRNA vessels, respectively. Conclusion A second dose of LV-shRNA-Vegf-A administration results in a moderate improvement in LVA at day 21.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The vessels were homogenized and the RNA was isolated using RNeasy mini kit (Qiagen) [5, 6]. The gene expression of interest was determined using RT-PCR analysis [6].…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

Janardhanan¹,

Yang²,

Kilari³

et al. 2016

Journal of Vascular and Interventional Radiology

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“…Finally, to truly and faithfully recapitulate the environment where "clinical" vascular access are created, our preclinical models studying AV access dysfunction must be evaluated in the setting of CKD. In rodent and porcine models in which AVFs and AVGs were created in the setting of CKD, mediators of oxidative stress, inflammation, and endothelial dysfunction are exacerbated at the level of the AVF, displaying decreased AVF blood flow and accelerating neointimal hyperplasia development (19,22,23,(53)(54)(55)(56).…”

Section: Novel Technologies and Strategies To Unravel Vascular Accessmentioning

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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The metalloproteinase ADAMTS1: A comprehensive review of its role in tumorigenic and metastatic pathways

Tan

Ricciardelli

Russell

2013

Intl Journal of Cancer

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As it was first characterized in 1997, the ADAMTS (A Disintegrin and Metalloprotease with ThromboSpondin motifs) metalloprotease family has been associated with many physiological and pathological conditions. Of the 19 proteases belonging to this family, considerable attention has been devoted to the role of its first member ADAMTS1 in cancer. Elevated ADAMTS1 promotes pro-tumorigenic changes such as increased tumor cell proliferation, inhibited apoptosis and altered vascularization. Importantly, it facilitates significant peritumoral remodeling of the extracellular matrix environment to promote tumor progression and metastasis. However, discrepancy exists, as several studies also depict ADAMTS1 as a tumor suppressor. This article reviews the current understanding of ADAMTS1 regulation and the consequence of its dysregulation in primary cancer and ADAMTS1-mediated pathways of cancer progression and metastasis.In cancer, the remodeling of the host tissue environment is fundamental for the dismantling of normal tissue structural constraints, establishment of vascular supply and invasion of metastatic cells. For this aberrant remodeling to occur, cancers cells rely on the proteolytic activity of extracellular matrix (ECM) proteases to facilitate the degradation of structural proteins that make up the ECM. 1,2 Metalloproteases belonging to the ADAMTS family have been widely implicated in tissue remodeling events manifested in cancer development, growth and progression. [3][4][5][6][7][8][9][10][11][12][13][14] There are 19 ADAMTS proteases identified in humans. They share homology in the catalytic ADAM-metalloprotease and disintegrin domains, but differ in the variable numbers of thrombospondin-like motifs and other carboxyl-terminal domains associated with ECM interaction. 15,16 Unlike the transmembrane ADAM family, ADAMTS proteases are secreted and bind to the ECM through their C-terminal regions. 17 33 Among them, the modulated expression of ADAMTS1 has been the most characterized in cancer and is the focus of this review.ADAMTS1 was initially described as a mediator of inflammation 34 but its activity has since become appreciated in organogenesis, [35][36][37][38] blood/lymph vessel formation, [39][40][41][42][43][44][45] ovarian folliculogenesis 39 and ovulation. 23,46 In these physiological events, ADAMTS1 remodels the ECM through the proteolytic degradation of key substrates such as chondroitin sulfated proteoglycans [47][48][49][50] and collagen. 51-53 ADAMTS1 also acts as an inhibitor of angiogenesis by sequestering proangioigenic stimuli, vascular epithelial growth factor (VEGF) and preventing its interaction with its receptor. 41,45 The dysregulation of ADAMTS1 often leads to pathological manifestations of altered ECM 54-56 and/or vascular density 57-60 and many studies have highlighted its functional activity during tumorigenic transformation. 14,[61][62][63][64][65][66][67] ADAMTS1 dysregulation is linked to four of the most commonly diagnosed cancers. But, conflicting reports currently surround its exp...

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Increased Expression of HIF-1α, VEGF-A and Its Receptors, MMP-2, TIMP-1, and ADAMTS-1 at the Venous Stenosis of Arteriovenous Fistula in a Mouse Model with Renal Insufficiency

Cited by 64 publications

References 31 publications

The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

The Role of Repeat Administration of Adventitial Delivery of Lentivirus-shRNA-Vegf-A in Arteriovenous Fistula to Prevent Venous Stenosis Formation

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

The metalloproteinase ADAMTS1: A comprehensive review of its role in tumorigenic and metastatic pathways

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