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Increased Matrix Metalloproteinase-9 Predicts Poor Wound Healing in Diabetic Foot Ulcers

  1. Yu Liu, MD1,
  2. Danqing Min, PhD2,
  3. Thyra Bolton3,
  4. Vanessa Nubé3,
  5. Stephen M. Twigg, PhD, MD1,2,3,
  6. Dennis K. Yue, PhD, MD1,2,3 and
  7. Susan V. McLennan, PhD (smclennan{at}med.usyd.edu.au)1,2
  1. 1Discipline of Medicine, University of Sydney, Sydney, Australia
  2. 2Department of Endocrinology, Royal Prince Alfred Hospital (RPAH), Sydney, Australia
  3. 3Diabetes Centre, Royal Prince Alfred Hospital (RPAH), Sydney, Australia

    Abstract

    Objective: We studied the relationship of diabetic ulcer wound fluid matrix metalloproteinase (MMPs), their tissue inhibitors (TIMPs) and Transforming Growth Factor -β1 (TGF-β1) with wound healing rate (WHR).

    Methods/Research Design: The ulcers were cleansed to remove exudates and wound fluids were collected for analysis of MMP-2 and -9, TIMP-1 and TGF-β1.

    Results: At presentation, MMP-9 and MMP-9/TIMP-1 ratio correlated inversely with WHR at 28 days (p<0.001). The MMP-9 and MMP-9/TIMP-1 ratio were lower in the 23 patients who achieved complete healing at 12 weeks versus the 39 that did not. The pro-MMP-9 concentration was predictive of healing within 12 weeks, addition of cutoffs for TIMP-1(>480pg/ml) and TGF-β (>115pg/ml) further improved its predictive power (AUC=0.94).

    Conclusions: These findings suggest that a milieu with high MMP-9 may be indicative of inflammation and poor wound healing. Measurements of MMP-9, TIMP-1 and TGF-β in wound fluid may help to identify ulcers at risk of poor healing

    Footnotes

      • Received April 21, 2008.
      • Accepted September 18, 2008.

    This Article

    1. Diabetes Care October 3, 2008
    1. All Versions of this Article:
      1. dc08-0763v1
      2. 32/1/117 most recent
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