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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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Related in: MedlinePlus

Wound area during the 12-week follow-up, expressed as a percentage of the initial area. The values correspond to medians for each group, with 25th and 75th percentiles. The number of patients whose wound is not completely healed is given in parentheses for each visit and each group. By week 8 7/7 patients had healed in the good healer group, whereas by week 12 3/9 patients had not healed in the poor healer group.
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fig01: Wound area during the 12-week follow-up, expressed as a percentage of the initial area. The values correspond to medians for each group, with 25th and 75th percentiles. The number of patients whose wound is not completely healed is given in parentheses for each visit and each group. By week 8 7/7 patients had healed in the good healer group, whereas by week 12 3/9 patients had not healed in the poor healer group.

Mentions: Sixteen Type 2 diabetic patients [mean age 64 years (range 47–84 years), 15 men and 1 woman] participated. The main characteristics of the two sub-groups (seven good healers and nine poor healers) are summarized in Table 1. The frequency of diabetes complications (neuropathy, retinopathy, nephropathy, arteriopathy of the lower limbs) was similar in the two groups. However, four patients who satisfied the inclusion criteria (at least one distal pulse) were later shown, by arterial Doppler, to have developed an IPS < 0.9 (respectively 0.4/0.5/0.8 and 0.84), suggesting arterial disease. Figure 1 shows the change in wound size in both groups during the 12 weeks of follow-up. All patients completed all the follow-up visits unless their wound healed completely before the end of the study. In the good healers group, all the wounds had completely closed before W12.


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)

Wound area during the 12-week follow-up, expressed as a percentage of the initial area. The values correspond to medians for each group, with 25th and 75th percentiles. The number of patients whose wound is not completely healed is given in parentheses for each visit and each group. By week 8 7/7 patients had healed in the good healer group, whereas by week 12 3/9 patients had not healed in the poor healer group.
© Copyright Policy
Related In: Results  -  Collection

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

fig01: Wound area during the 12-week follow-up, expressed as a percentage of the initial area. The values correspond to medians for each group, with 25th and 75th percentiles. The number of patients whose wound is not completely healed is given in parentheses for each visit and each group. By week 8 7/7 patients had healed in the good healer group, whereas by week 12 3/9 patients had not healed in the poor healer group.
Mentions: Sixteen Type 2 diabetic patients [mean age 64 years (range 47–84 years), 15 men and 1 woman] participated. The main characteristics of the two sub-groups (seven good healers and nine poor healers) are summarized in Table 1. The frequency of diabetes complications (neuropathy, retinopathy, nephropathy, arteriopathy of the lower limbs) was similar in the two groups. However, four patients who satisfied the inclusion criteria (at least one distal pulse) were later shown, by arterial Doppler, to have developed an IPS < 0.9 (respectively 0.4/0.5/0.8 and 0.84), suggesting arterial disease. Figure 1 shows the change in wound size in both groups during the 12 weeks of follow-up. All patients completed all the follow-up visits unless their wound healed completely before the end of the study. In the good healers group, all the wounds had completely closed before W12.

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