Experimental murine arteriovenous fistula model to study restenosis after transluminal angioplasty

Abstract

Percutaneous transluminal angioplasty (PTA) is a very common interventional treatment for treating stenosis in arteriovenous fistula (AVF) used for hemodialysis vascular access. Restenosis occurs after PTA, resulting in vascular lumen loss and a decrease in blood flow. Experimental animal models have been developed to study the pathogenesis of stenosis, but there is no restenosis model after PTA of stenotic AVF in mice. Here, we describe the creation of a murine model of restenosis after angioplasty of a stenosis in an AVF. The murine restenosis model has several advantages, including the rapid development of restenotic lesions in the vessel after angioplasty and the potential to evaluate endovascular and perivascular therapeutics for treating restenosis. The protocol includes a detailed description of the partial nephrectomy procedure to induce chronic kidney disease, the AVF procedure for development of de novo stenosis and the angioplasty treatment associated with progression of restenosis. We monitored the angioplasty-treated vessel for vascular patency and hemodynamic changes for a period of 28 d using ultrasound. Vessels were collected at different time points and processed for histological analysis and immunostaining. This angioplasty model, which can be performed with basic microvascular surgery skills, could be used to identify potential endovascular and perivascular therapies to reduce restenosis after angioplasty procedures.

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Fig. 1: Materials required and technical procedures for CKD, AVF and angioplasty procedures.
Fig. 2: Time course of histomorphometric changes after the angioplasty procedure.
Fig. 3: Immunostaining for endothelial cells (CD31+ cells) at different time points.
Fig. 4: Immunostaining for smooth muscle cells (α-SMA+ cells) at different time points.
Fig. 5: Immunostaining for cellular proliferation (Ki-67) at different time points.
Fig. 6: Drug delivery using perivascular and endovascular methods in the murine angioplasty model.

Data availability

The data that support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

The authors acknowledge the assistance of Lucy Bahn, PhD for editing the manuscript. This research was supported by NIH grants to S.M. (HL098967 and DK107870).

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Authors

Contributions

C.C. contributed to study design, animal surgeries, data collection, interpretation of data, and manuscript preparation. C.Z. contributed to study design, data analysis, and manuscript preparation. S.K. contributed to study design, interpretation of data, and manuscript review. A.S., A.K.S., M.L.S., A.M., and Y.L. contributed to interpretation of data, and manuscript review. S.M. contributed as a guarantor and to study design, interpretation of data and manuscript editing.

Corresponding author

Correspondence to Sanjay Misra.

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The authors declare no competing interests.

Supplementary information

Supplementary Information

Supplementary Figs. 1 and 2 and legends for Supplementary Videos 1 and 2.

Reporting Summary

Supplementary Video 1

Technique for AVF creation by anastomosing the end of the right external jugular vein to the side of the left common carotid artery in a mouse. All animal experiments were approved by the Institutional Animal Care and Use Committee of Mayo Clinic.

Supplementary Video 2

Technique for the angioplasty procedure in a stenotic arterialized external jugular vein by using a 1.25 mm × 6 mm coronary artery balloon catheter in a mouse. All animal experiments were approved by the Institutional Animal Care and Use Committee of Mayo Clinic.

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Cai, C., Zhao, C., Kilari, S. et al. Experimental murine arteriovenous fistula model to study restenosis after transluminal angioplasty. Lab Anim 49, 320–334 (2020). https://doi.org/10.1038/s41684-020-00659-x

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