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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2015
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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. |
format | Online Article Text |
id | pubmed-4534710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
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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