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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

Levels of MMP-1 and TIMP-1 for good and poor healers during the 12-week follow-up period (results are expressed as medians with 25th and 75th percentiles).
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fig03: Levels of MMP-1 and TIMP-1 for good and poor healers during the 12-week follow-up period (results are expressed as medians with 25th and 75th percentiles).

Mentions: Initial levels of the different MMPs are shown in Table 2. There were no significant differences in any parameter between the two groups. During the 12 weeks of follow-up, the changing profile of MMPs differed between groups (Figs 2 and 3). Figure 2 shows that MMP-8 and -9 levels in good healers remained stable between W0 and W2, before starting to decrease from W2 onwards. The change in MMP-9 levels between W0 and W4 did not reach significance (P = 0.14). In contrast, in poor healers MMP-8 and -9 levels remained constant throughout the follow-up period. Moreover (Table 2 and Fig. 3), the level of MMP-1 was significantly higher at W0 in good healers compared to poor healers at week 2 [4.78 pg/µg of protein (CI 1.9–7.65) vs. 2.27 pg/µg (CI 1.24–0.29); P = 0.039]. MMP-1 level in good healers appeared to diminish during the study whereas it remained stable in poor healers. Over the same follow-up period, there was no significant difference in the TIMP-1 level between the two groups.


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)

Levels of MMP-1 and TIMP-1 for good and poor healers during the 12-week follow-up period (results are expressed as medians with 25th and 75th percentiles).
© Copyright Policy
Related In: Results  -  Collection

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

fig03: Levels of MMP-1 and TIMP-1 for good and poor healers during the 12-week follow-up period (results are expressed as medians with 25th and 75th percentiles).
Mentions: Initial levels of the different MMPs are shown in Table 2. There were no significant differences in any parameter between the two groups. During the 12 weeks of follow-up, the changing profile of MMPs differed between groups (Figs 2 and 3). Figure 2 shows that MMP-8 and -9 levels in good healers remained stable between W0 and W2, before starting to decrease from W2 onwards. The change in MMP-9 levels between W0 and W4 did not reach significance (P = 0.14). In contrast, in poor healers MMP-8 and -9 levels remained constant throughout the follow-up period. Moreover (Table 2 and Fig. 3), the level of MMP-1 was significantly higher at W0 in good healers compared to poor healers at week 2 [4.78 pg/µg of protein (CI 1.9–7.65) vs. 2.27 pg/µg (CI 1.24–0.29); P = 0.039]. MMP-1 level in good healers appeared to diminish during the study whereas it remained stable in poor healers. Over the same follow-up period, there was no significant difference in the TIMP-1 level between the two groups.

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