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 journalArticlepeer-review

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)108-15
Number of pages8
JournalVascular pharmacology
Volume71
DOIs
Publication statusPublished - Aug 2015

Keywords

  • AMP-Activated Protein Kinases
  • Administration, Cutaneous
  • Arteriovenous Fistula
  • Cell Proliferation
  • Cells, Cultured
  • Diclofenac
  • Drug Delivery Systems
  • Hyperplasia
  • Neointima
  • Vascular Patency

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