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Matrix metalloproteinases and diabetic foot ulcers: the ratio of MMP-1 to TIMP-1 is a predictor of wound healing.

Muller M, Trocme C, Lardy B, Morel F, Halimi S, Benhamou PY - Diabet. Med. (2008)

Bottom Line: Results were analysed by the degree of wound healing: good healers (defined by a reduction of at least 82% in initial wound surface at 4 weeks) and poor healers (reduction of less than 82% in wound surface at 4 weeks).In good healers, levels of MMP-8 and -9 secreted by inflammatory cells decreased earlier.There was a significant correlation between a high ratio of MMP-1/TIMP-1 and good healing (r = 0.65, P = 0.008).

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Endocrinology, University Hospital, Grenoble, France.

ABSTRACT

Aims: Matrix metalloproteinases (MMPs) play a major role in wound healing: they can degrade all components of the extracellular matrix. In diabetic foot ulcers there is an excess of MMPs and a decrease of the tissue inhibitors of MMPs (TIMPs). This imbalance is probably one cause of impaired healing. However, little is known about changes in MMPs during wound healing.

Methods: Sixteen patients with neuropathic diabetic foot ulcers participated. Wound fluid was collected regularly during the 12-week follow-up period, for measurement of MMP-1, MMP-2, MMP-8, MMP-9 and TIMP-1. Results were analysed by the degree of wound healing: good healers (defined by a reduction of at least 82% in initial wound surface at 4 weeks) and poor healers (reduction of less than 82% in wound surface at 4 weeks).

Results: In good healers, levels of MMP-8 and -9 secreted by inflammatory cells decreased earlier. The initial levels of MMP-1 were similar in good and poor healers (P = 0.1) but rose significantly at week 2 in good healers (P = 0.039). There was a significant correlation between a high ratio of MMP-1/TIMP-1 and good healing (r = 0.65, P = 0.008). Receiver Operator Curve (ROC) analysis showed that an MMP-1/TIMP-1 ratio of 0.39 best predicted wound healing (sensitivity = 71%, specificity = 87.5%).

Conclusions: A high level of MMP-1 seems essential to wound healing, while an excess of MMP-8 and -9 is deleterious, and could be a target for new topical treatments. The MMP-1/TIMP-1 ratio is a predictor of wound healing in diabetic foot ulcers.

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The ratio of MMP-1/TIMP-1 is a predictive factor for healing. The ROC analysis gives an area under the curve of 0.821 [confidence interval (CI) 0.6–1.04]. A ratio of 0.39 at week 0 has a sensitivity of 71% and a specificity of 87.5% for detecting a wound area reduction of at least 82% at week 4 (and thus predicting wound healing at week 12).
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fig04: The ratio of MMP-1/TIMP-1 is a predictive factor for healing. The ROC analysis gives an area under the curve of 0.821 [confidence interval (CI) 0.6–1.04]. A ratio of 0.39 at week 0 has a sensitivity of 71% and a specificity of 87.5% for detecting a wound area reduction of at least 82% at week 4 (and thus predicting wound healing at week 12).

Mentions: The ROC curve showed that an MMP-1/TIMP-1 ratio at W0 of 0.39 best predicts a reduction in wound area of at least 82% at W4—i.e. predicts complete wound healing at W12—with a sensitivity of 71% and a specificity of 87.5% (Fig. 4). Logistic regression analysis showed that this ratio at W0 is a predictive factor a priori independent of the wound area and depth. However, in view of the small number of patients, the results from this multivariate model should be treated with caution.


Matrix metalloproteinases and diabetic foot ulcers: the ratio of MMP-1 to TIMP-1 is a predictor of wound healing.

Muller M, Trocme C, Lardy B, Morel F, Halimi S, Benhamou PY - Diabet. Med. (2008)

The ratio of MMP-1/TIMP-1 is a predictive factor for healing. The ROC analysis gives an area under the curve of 0.821 [confidence interval (CI) 0.6–1.04]. A ratio of 0.39 at week 0 has a sensitivity of 71% and a specificity of 87.5% for detecting a wound area reduction of at least 82% at week 4 (and thus predicting wound healing at week 12).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2326726&req=5

fig04: The ratio of MMP-1/TIMP-1 is a predictive factor for healing. The ROC analysis gives an area under the curve of 0.821 [confidence interval (CI) 0.6–1.04]. A ratio of 0.39 at week 0 has a sensitivity of 71% and a specificity of 87.5% for detecting a wound area reduction of at least 82% at week 4 (and thus predicting wound healing at week 12).
Mentions: The ROC curve showed that an MMP-1/TIMP-1 ratio at W0 of 0.39 best predicts a reduction in wound area of at least 82% at W4—i.e. predicts complete wound healing at W12—with a sensitivity of 71% and a specificity of 87.5% (Fig. 4). Logistic regression analysis showed that this ratio at W0 is a predictive factor a priori independent of the wound area and depth. However, in view of the small number of patients, the results from this multivariate model should be treated with caution.

Bottom Line: Results were analysed by the degree of wound healing: good healers (defined by a reduction of at least 82% in initial wound surface at 4 weeks) and poor healers (reduction of less than 82% in wound surface at 4 weeks).In good healers, levels of MMP-8 and -9 secreted by inflammatory cells decreased earlier.There was a significant correlation between a high ratio of MMP-1/TIMP-1 and good healing (r = 0.65, P = 0.008).

View Article: PubMed Central - PubMed

Affiliation: Department of Nephrology and Endocrinology, University Hospital, Grenoble, France.

ABSTRACT

Aims: Matrix metalloproteinases (MMPs) play a major role in wound healing: they can degrade all components of the extracellular matrix. In diabetic foot ulcers there is an excess of MMPs and a decrease of the tissue inhibitors of MMPs (TIMPs). This imbalance is probably one cause of impaired healing. However, little is known about changes in MMPs during wound healing.

Methods: Sixteen patients with neuropathic diabetic foot ulcers participated. Wound fluid was collected regularly during the 12-week follow-up period, for measurement of MMP-1, MMP-2, MMP-8, MMP-9 and TIMP-1. Results were analysed by the degree of wound healing: good healers (defined by a reduction of at least 82% in initial wound surface at 4 weeks) and poor healers (reduction of less than 82% in wound surface at 4 weeks).

Results: In good healers, levels of MMP-8 and -9 secreted by inflammatory cells decreased earlier. The initial levels of MMP-1 were similar in good and poor healers (P = 0.1) but rose significantly at week 2 in good healers (P = 0.039). There was a significant correlation between a high ratio of MMP-1/TIMP-1 and good healing (r = 0.65, P = 0.008). Receiver Operator Curve (ROC) analysis showed that an MMP-1/TIMP-1 ratio of 0.39 best predicted wound healing (sensitivity = 71%, specificity = 87.5%).

Conclusions: A high level of MMP-1 seems essential to wound healing, while an excess of MMP-8 and -9 is deleterious, and could be a target for new topical treatments. The MMP-1/TIMP-1 ratio is a predictor of wound healing in diabetic foot ulcers.

Show MeSH
Related in: MedlinePlus