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

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 u...

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Autores principales: MacAskill, Mark G., Watson, David G., Ewart, Marie-Ann, Wadsworth, Roger, Jackson, Andrew, Aitken, Emma, MacKenzie, Graeme, Kingsmore, David, Currie, Susan, Coats, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534710/
https://www.ncbi.nlm.nih.gov/pubmed/25866325
http://dx.doi.org/10.1016/j.vph.2015.02.012
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author MacAskill, Mark G.
Watson, David G.
Ewart, Marie-Ann
Wadsworth, Roger
Jackson, Andrew
Aitken, Emma
MacKenzie, Graeme
Kingsmore, David
Currie, Susan
Coats, Paul
author_facet MacAskill, Mark G.
Watson, David G.
Ewart, Marie-Ann
Wadsworth, Roger
Jackson, Andrew
Aitken, Emma
MacKenzie, Graeme
Kingsmore, David
Currie, Susan
Coats, Paul
author_sort MacAskill, Mark G.
collection PubMed
description 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.
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spelling pubmed-45347102015-08-13 Improving arteriovenous fistula patency: Transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation MacAskill, Mark G. Watson, David G. Ewart, Marie-Ann Wadsworth, Roger Jackson, Andrew Aitken, Emma MacKenzie, Graeme Kingsmore, David Currie, Susan Coats, Paul Vascul Pharmacol Article 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. Elsevier Science 2015-08 /pmc/articles/PMC4534710/ /pubmed/25866325 http://dx.doi.org/10.1016/j.vph.2015.02.012 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
MacAskill, Mark G.
Watson, David G.
Ewart, Marie-Ann
Wadsworth, Roger
Jackson, Andrew
Aitken, Emma
MacKenzie, Graeme
Kingsmore, David
Currie, Susan
Coats, Paul
Improving arteriovenous fistula patency: Transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation
title Improving arteriovenous fistula patency: Transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation
title_full Improving arteriovenous fistula patency: Transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation
title_fullStr Improving arteriovenous fistula patency: Transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation
title_full_unstemmed Improving arteriovenous fistula patency: Transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation
title_short Improving arteriovenous fistula patency: Transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation
title_sort improving arteriovenous fistula patency: transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via ampk activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534710/
https://www.ncbi.nlm.nih.gov/pubmed/25866325
http://dx.doi.org/10.1016/j.vph.2015.02.012
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