Improving arteriovenous fistula patency

transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation

Mark G. MacAskill, David G. Watson, Marie-Ann Ewart, Roger Wadsworth, Andrew Jackson, Emma Aitken, Graeme MacKenzie, David Kingsmore, Susan Currie, Paul Coats

Research output: Contribution to journalArticle

2 Citations (Scopus)
122 Downloads (Pure)

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 12months. 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.

Original languageEnglish
Pages (from-to)108-115
Number of pages8
JournalVascular pharmacology
Volume71
Early online date10 Apr 2015
DOIs
Publication statusPublished - 1 Aug 2015

Fingerprint

AMP-Activated Protein Kinases
Diclofenac
Arteriovenous Fistula
Catheterization
Hyperplasia
Blood Vessels
Anti-Inflammatory Agents
Cell Cycle Proteins
Cyclin D1
Non-Steroidal Anti-Inflammatory Agents
Renal Dialysis
Rabbits
Wounds and Injuries

Keywords

  • vascular
  • re-stenosis
  • cell proliferation
  • pharmacotherapy

Cite this

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. In: Vascular pharmacology. 2015 ; Vol. 71. pp. 108-115.
@article{968002b9914b415aa8ecea7af60ffc82,
title = "Improving arteriovenous fistula patency: transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation",
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 12months. 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.",
keywords = "vascular, re-stenosis, cell proliferation, pharmacotherapy",
author = "MacAskill, {Mark G.} and Watson, {David G.} and Marie-Ann Ewart and Roger Wadsworth and Andrew Jackson and Emma Aitken and Graeme MacKenzie and David Kingsmore and Susan Currie and Paul Coats",
year = "2015",
month = "8",
day = "1",
doi = "10.1016/j.vph.2015.02.012",
language = "English",
volume = "71",
pages = "108--115",
journal = "Vascular pharmacology",
issn = "1537-1891",

}

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.

In: Vascular pharmacology, Vol. 71, 01.08.2015, p. 108-115.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Improving arteriovenous fistula patency

T2 - transdermal delivery of diclofenac reduces cannulation-dependent neointimal hyperplasia via AMPK activation

AU - MacAskill, Mark G.

AU - Watson, David G.

AU - Ewart, Marie-Ann

AU - Wadsworth, Roger

AU - Jackson, Andrew

AU - Aitken, Emma

AU - MacKenzie, Graeme

AU - Kingsmore, David

AU - Currie, Susan

AU - Coats, Paul

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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 12months. 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.

AB - 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 12months. 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.

KW - vascular

KW - re-stenosis

KW - cell proliferation

KW - pharmacotherapy

UR - http://www.scopus.com/inward/record.url?scp=84937971884&partnerID=8YFLogxK

UR - http://www.sciencedirect.com/science/journal/15371891

U2 - 10.1016/j.vph.2015.02.012

DO - 10.1016/j.vph.2015.02.012

M3 - Article

VL - 71

SP - 108

EP - 115

JO - Vascular pharmacology

JF - Vascular pharmacology

SN - 1537-1891

ER -