Improving arteriovenous fistula patency: transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation

MacAskill, M., Watson, D. G., Ewart, M.-A., Wadsworth, R., Jackson, A., Aitken, E., MacKenzie, G., Kingsmore, D., Currie, S. and Coats, P. (2015) Improving arteriovenous fistula patency: transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation. Vascular Pharmacology, 71, pp. 108-115. (doi: 10.1016/j.vph.2015.02.012) (PMID:25866325) (PMCID:PMC4534710)

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Abstract

Creation of an autologous arteriovenous fistula (AVF) for vascular access in haemodialysis is the modality of choice. However neointimal hyperplasia and loss of the luminal compartment result in AVF patency rates of ~ 60% at 12 months. The exact cause of neointimal hyperplasia in the AVF is poorly understood. Vascular trauma has long been associated with hyperplasia. With this in mind in our rabbit model of AVF we simulated cannulation autologous to that undertaken in vascular access procedures and observed significant neointimal hyperplasia as a direct consequence of cannulation. The neointimal hyperplasia was completely inhibited by topical transdermal delivery of the non-steroidal anti-inflammatory (NSAID) diclofenac. In addition to the well documented anti-inflammatory properties we have identified novel anti-proliferative mechanisms demonstrating diclofenac increases AMPK-dependent signalling and reduced expression of the cell cycle protein cyclin D1. In summary prophylactic transdermal delivery of diclofenac to the sight of AVF cannulation prevents adverse neointimal hyperplasic remodelling and potentially offers a novel treatment option that may help prolong AVF patency and flow rates.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ewart, Dr Marie-Ann and Kingsmore, Professor David
Authors: MacAskill, M., Watson, D. G., Ewart, M.-A., Wadsworth, R., Jackson, A., Aitken, E., MacKenzie, G., Kingsmore, D., Currie, S., and Coats, P.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Vascular Pharmacology
Publisher:Elsevier Inc.
ISSN:1537-1891
ISSN (Online):1879-3649
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Vascular Pharmacology 71:108-115
Publisher Policy:Reproduced under a Creative Commons License

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