The Mouse Aortocaval Fistula Model with Intraluminal Drug Delivery

Isaji, Toshihiko; Dardik, Alan

doi:10.1007/978-1-4939-8597-5_21

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…Fistula patency was identified based on a low-resistance arterial waveform characterized by persistent, disturbed diastolic flow. 21,22 Drug delivery in vivo Recombinant His tag-labeled EphB4-Fc (30 mL of 1 mg/mL solution; R&D Systems, catalog # 446-B4) or control-Fc (30 mL of 1 mg/mL solution; R&D Systems, catalog # 110-HG-100) was premixed with F-127 Pluronic hydrogel (90 mL of 25% w/v; Sigma-Aldrich, catalog # 9003-11-6) and placed on ice. After AVF creation and confirmation of hemostasis, the drug mixture (120 mL) was applied onto the adventitia of the infrarenal IVC, covering the anterior and lateral surfaces and including the AVF site, and incubated for 5 min as previously described.…”

Section: Ultrasound Measurementsmentioning

confidence: 99%

Activation of EphrinB2 Signaling Promotes Adaptive Venous Remodeling in Murine Arteriovenous Fistulae

Wang

Liu

et al. 2021

Journal of Surgical Research

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Background: Arteriovenous fistulae (AVF) are the preferred mode of vascular access for hemodialysis. Before use, AVF remodel by thickening and dilating to achieve a functional conduit via an adaptive process characterized by expression of molecular markers characteristic of both venous and arterial identity. Although signaling via EphB4, a determinant of venous identity, mediates AVF maturation, the role of its counterpart EphrinB2, a determinant of arterial identity, remains unclear. We hypothesize that EphrinB2 signaling is active during AVF maturation and may be a mechanism of venous remodeling. Methods: Aortocaval fistulae were created or sham laparotomy was performed in C57Bl/6 mice, and specimens were examined on Days 7 or 21. EphrinB2 reverse signaling was activated with EphB4-Fc applied periadventitially in vivo and in endothelial cell culture medium in vitro. Downstream signaling was assessed using immunoblotting and immunofluorescence. Results: Venous remodeling during AVF maturation was characterized by increased expression of EphrinB2 as well as Akt1, extracellular signal-regulated kinases 1/2 (ERK1/ 2), and p38. Activation of EphrinB2 with EphB4-Fc increased phosphorylation of Eph-rinB2, endothelial nitric oxide synthase, Akt1, ERK1/2, and p38 and was associated with increased diameter and wall thickness in the AVF. Both mouse and human endothelial cells treated with EphB4-Fc increased phosphorylation of EphrinB2, endothelial nitric oxide synthase, Akt1, ERK1/2, and p38 and increased endothelial cell tube formation and migration. Conclusions: Activation of EphrinB2 signaling by EphB4-Fc was associated with adaptive venous remodeling in vivo while activating endothelial cell function in vitro.

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Section: Ultrasound Measurementsmentioning

confidence: 99%

Activation of EphrinB2 Signaling Promotes Adaptive Venous Remodeling in Murine Arteriovenous Fistulae

Wang

Liu

et al. 2021

Journal of Surgical Research

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“…This model is well established (also in different species and different target vessels) to study restenosis and neointimal formation, especially in terms of venous remodeling. It is distinguished by rapid lesion development and can be performed as required with or without a renal disease background ( 68 , 69 ).…”

Section: Mouse Models Of Neointimal Hyperplasiamentioning

confidence: 99%