Evolution of Shear Stress, Protein Expression, and Vessel Area in an Animal Model of Arterial Dilatation in Hemodialysis Grafts

Misra, Sanjay; Fu, Alex A.; Misra, Khamal D.; Glockner, James F.; Mukhopadyay, Debabrata

doi:10.1016/j.jvir.2009.09.024

Cited by 18 publications

(17 citation statements)

References 38 publications

(68 reference statements)

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“…Similarly, in carotid artery ligation model in mice, MMP-2 expression apparently increased at day 7 and proceeds to increase even 4weeks after vascular injury (9). This evidences show that MMP-2 and MMP-9 have different expression patterns in at different time points (27). But, in our study we demonstrated that MMP-2 and MMP-9 expressions appear to be similar at day 28 after vascular injury in rabbit model of carotid anastomosis.…”

Section: Discussionsupporting

confidence: 65%

The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model

Guzeloglu¹,

Gül²,

Reel³

et al. 2011

Anadolu Kardiyol Derg

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ÖZETAmaç: Çalışmamızın amacı tavşan karotis arter anastomoz modelinde gelişen neointimal hiperplazi üzerine bir matriks metalloproteinaz inhibitörü olarak zoledronik asidin (ZA) etkilerini araştırmaktır. Yöntemler: Bu deneysel çalışmada Yeni Zelanda tipi erkek tavşanlar plasebo ve ilaç-tedavi olmak üzere iki gruba ayrılmıştır. Anestezi sonrası, her bir tavşanın sağ karotis arteri 8/0 polipropilen sütür ile uç uca anastomoz edilmiştir. Sol karotis arter ise uygulama olmaksızın kontrol olarak bırakılmıştır. Plasebo grubundaki tavşanlara (n=6) operasyon sonrası 28 gün boyunca PBS (0.5mL/kg/gün/s.k.) uygulanırken ilaç grubundaki tavşanlara (n=6) aynı süre boyunca zoledronik asid (100 μg/kg/gün/s.k.) uygulanmıştır. Sakrifikasyondan sonra anastomozlu ve kontrol arterler izole edilmiştir. Morfometrik ve immünohistokimyasal incelemeler gerçekleştirilmiştir. Morfometrik ve immünohistokimyasal verilerin istatistiksel analizleri sırasıyla çift yönlü ANOVA ve Ki-kare testi ile yapılmıştır. Bulgular: PBS grubunda anastomozlu arterlerde oluşan damar hasarının, kontrol artere kıyasla intimal alanı (kontrol: 22.62±4.26, μm 2 *1000 anastomozlu: 112.51±61.18 μm 2 *1000, p<0.01) ve intima/media indeksini (kontrol: 0.075±0.01, anastomozlu: 0.347±0.29, p<0.05) istatistiksel olarak anlamlı şekilde artırdığı saptanmıştır. Zoledronik asidin, PBS grubuna kıyasla intimal alanı (39.29±18.21 μm 2 *1000, p<0.01) ve intima/media indeksini (0.112±0.07, p<0.05) anlamlı şekilde azaltmıştır. Buna ek olarak, ZA grubundan anastomozlu arterlerde α-düz kas aktin immunpozitivitesi ABSTRACT Objective: The aim of the present study was to investigate the effect of zoledronic acid (ZA), as a matrix metalloproteinase inhibitor, on neointimal hyperplasia in rabbit carotid anastomosis model. Methods: New Zealand male rabbits were divided into two groups as placebo and treatment groups in this experimental study. After anesthesia, the right carotid artery of each rabbit was end-to-end anastomosed with an 8/0 polypropylene suture. Left carotid artery was kept as control without any operation. Placebo group (n=6) received phosphate buffered saline (PBS) (0.5mL/kg/day/s.c.) for 28 days postoperatively, whereas ZA group (n=6) received ZA (100 μg/kg/day/s.c.) for the same period. After sacrification, the anastomosed and control arteries were isolated. Morphometric and immunohistochemical examinations were performed. Statistical analyses of morphometric and immunohistochemical data were performed using two-way ANOVA and Chi-square test respectively. Results: In PBS group, vascular injury in the anastomosed artery significantly increased the intimal area (anastomosed: 112.51±61.18 μm 2 *1000 vs. control: 22.62±4.26μm 2 *1000, p<0.01) and intima/media index (anastomosed: 0.347±0.29 vs. control: 0.075±0.01, p<0.05) compared to control artery. ZA significantly reduced the intimal area (39.29±18.21 μm 2 *1000 , p<0.01) and intima/media index (0.112±0.07, p<0.05) compared to PBS group. Additionally, α-smooth muscle actin immunopositivity was found significantly decrease...

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Section: Discussionsupporting

confidence: 65%

The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model

Guzeloglu¹,

Gül²,

Reel³

et al. 2011

Anadolu Kardiyol Derg

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“…[100, 109] MMP-2 and MMP-9, referred to as gelatinases due to their ability to break down gelatin and several other collagens in particular the type IV collagen of the basement membrane, are upregulated within as little as 3 hours after venous implantation. [43, 111-113] Ultrastructural studies have documented progressive loss of type IV collagen in the early bypass graft indicating destruction of basement membrane (BM) which normally surrounds 95% of saphenous vein medial SMCs. [114, 115] The SMC BM not only represents a physical barrier to SMC migration but focal contacts between SMC and BM laminin keeps the cell in a quiescent, differentiated phenotype.…”

Section: Molecular Remodelingmentioning

confidence: 99%

Vein graft failure

Owens

Gasper

Rahman

et al. 2015

Journal of Vascular Surgery

119

107

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Following the creation of an autogenous lower extremity bypass graft, the vein must undergo a series of dynamic structural changes to stabilize the arterial hemodynamic forces. These changes, commonly referred to as remodeling, include an inflammatory response, the development of a neointima, matrix turnover, and cellular proliferation and apoptosis. The sum total of these processes results in dramatic alterations in the physical and biomechanical attributes of the arterialized vein. The most clinically obvious and easily measured of these is lumen remodeling of the graft. However, though somewhat less precise, wall thickness, matrix composition, and endothelial changes can be measured in vivo within the healing vein graft. Recent translational work has demonstrated the clinical relevance of remodeling as it relates to vein graft patency and the systemic factors influencing it. By correlating histologic and molecular changes in the vein, insights into potential therapeutic strategies to prevent bypass failure and areas for future investigation are explored.

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“…Many different remnant kidney animal models have been used to study the mechanism of chronic kidney disease (17-24). We used the murine model of chronic kidney disease to determine the changes in several important profibrotic genes.…”

Section: Discussionmentioning

confidence: 99%

“…Many different animals have been used for this model including rats, mice, rabbits, cats, dogs, baboons, and pigs (17-24). The purpose of the current report was to determine the expression pattern of a disintegrin and metalloproteinase with thrombospondin motif-1 (ADAMTS-1), MMP-2, MMP-9, and its inhibitors along with fibroblast specific protein-1 (FSP-1) in a murine remnant kidney model.…”

Section: Introductionmentioning

confidence: 99%

Expression of Profibrotic Genes in a Murine Remnant Kidney Model

Yang

Vohra

Janardhanan

et al. 2011

Journal of Vascular and Interventional Radiology

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PURPOSE To test the hypothesis that there is increased expression of several profibrotic genes including matrix metalloproteinase–2 (MMP-2), and -9 (MMP-9), and its inhibitors (TIMP-1 and TIMP-2), a disintegrin and metalloproteinase with thrombospondin motif -1 (ADAMTS-1), and fibroblast specific protein-1 (FSP-1) in a murine remnant kidney (RK) model. MATERIALS AND METHODS CKD was created in ten C57BL/6 male mice (20-25 g) by performing a right nephrectomy and ligation of the upper pole of the left kidney (RK). Animals were sacrificed at 42 and 56 days later. Real time polymerase chain reaction (RT-PCR) for MMP-2, MMP-9, TIMP-1, TIMP-2, ADAMTS-1, and FSP-1 was performed in the RK. Histologic evaluation of the RK was performed using Ki-67, α-smooth muscle cell actin (α-SMA), hematoxylin and eosin, and Masson’s trichrome staining. Kidney function was assessed using serum BUN and creatinine. RESULTS The mean serum BUN and creatinine levels at day 42 and 56 were significantly higher than baseline (P <0 .05). By day 42, the mean expression of MMP-2, MMP-9, TIMP-1, ADAMTS-1, and FSP-1 was significantly higher in the RK when compared to normal kidney (P<0.05) and by day 56, only FSP-1 expression increased significantly higher (P<0.05). There was increased fibrosis by Masson’s trichrome, increased Ki-67, with increased α-SMA staining in the RK when compared to normal kidneys. CONCLUSIONS In the RK, there was increased fibrosis with increased α -SMA and Ki-67 staining with significantly increased expression of MMP-2, MMP-9, TIMP-1, ADAMTS-1, and FSP-1.

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Evolution of Shear Stress, Protein Expression, and Vessel Area in an Animal Model of Arterial Dilatation in Hemodialysis Grafts

Cited by 18 publications

References 38 publications

The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model

The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model

Vein graft failure

Expression of Profibrotic Genes in a Murine Remnant Kidney Model

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