Expression of active matrix metalloproteinase-9 as a likely contributor to the clinical failure of aclerastide in treatment of diabetic foot ulcers

Article

Abstract

Chronic wounds are a complication of diabetes. Treatment for diabetic foot ulcers is complex with little clinical recourse, resulting in 108,000 lower-limb amputations annually in the United States alone. Matrix metalloproteinases (MMPs) play important roles in the pathology and in the repair of chronic wounds. We previously identified active MMP-8 and MMP-9 in wounds of diabetic mice and determined that MMP-8 accelerates wound repair, while MMP-9 is the culprit for the diabetic wound being refractory to healing. Aclerastide, a peptide analog of angiotensin II, recently failed in phase III clinical trials for treatment of diabetic foot ulcers. We demonstrate herein that treatment of wounds of diabetic mice with aclerastide results in elevated levels of reactive oxygen species and of active MMP-9, which is likely an important contributor to the failure of aclerastide in clinical trials.

Attributes

Attribute NameValues
Creator
  • Trung T. Nguyen

  • Derong Ding

  • William R. Wolter

  • Matthew M. Champion

  • Dusan Hesek

  • Mijoon Lee

  • Rocio L. Pérez

  • Valerie A. Schroeder

  • Mark A. Suckow

  • Shahriar Mobashery

  • Mayland Chang

Publication Date
  • 2018

Date Created
  • 2018-08-23

Language
  • English

Departments and Units
Record Visibility Public
Content License
  • All rights reserved

Digital Object Identifier

doi:10.1016/j.ejphar.2018.07.014

This DOI is the best way to cite this article.