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Abnormal Extracellular Matrix Metabolism in Chronically Ischemic Skin: A Mechanism for Dermal Failure in Leg Ulcers  Stephen J. Dalton, David C. Mitchell,

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Presentation on theme: "Abnormal Extracellular Matrix Metabolism in Chronically Ischemic Skin: A Mechanism for Dermal Failure in Leg Ulcers  Stephen J. Dalton, David C. Mitchell,"— Presentation transcript:

1 Abnormal Extracellular Matrix Metabolism in Chronically Ischemic Skin: A Mechanism for Dermal Failure in Leg Ulcers  Stephen J. Dalton, David C. Mitchell, Christine V. Whiting, John F. Tarlton  Journal of Investigative Dermatology  Volume 125, Issue 2, Pages (August 2005) DOI: /j X x Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

2 Figure 1 Collagen synthesis in the ischemic samples expressed as a percentage of the matched non-ischemic values. Ischemic skin had significantly higher collagen synthesis than the paired non-ischemic tissue (p= Wilcoxon's signed-rank test). Journal of Investigative Dermatology  , DOI: ( /j X x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

3 Figure 2 Collagen synthesis expressed as type I collagen C propeptide (PICP) levels (ng per mg) of ischemic, non-ischemic, and controls (varicose vein (VV) and total knee replacement (TKR)). Comparing ischemic with non-ischemic (p= Wilcoxon's signed-rank test), ischemic and VV (p<0.005), and ischemic with TKR (p<0.01) (unpaired t test with Welch correction). Error bars showing standard error of mean. No statistical difference was found between VV, TKR, and non-ischemic samples (p>0.5 unpaired t test with Welch correction). Journal of Investigative Dermatology  , DOI: ( /j X x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

4 Figure 3 Total collagen content of sample as determined from hydroxyproline analysis. No difference was detected in the collagen content between ischemic and non-ischemic skin (a) in individual ischemic samples expressed as a percentage of the matched non-ischemic values, and (b) grouped non-ischemic compared with ischemic samples, expressed as % collagen. Error bars expressing standard error of mean (p>0.5 Wilcoxon's signed-rank test). Journal of Investigative Dermatology  , DOI: ( /j X x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

5 Figure 4 Example of (a), matrix metalloproteinase (MMP) zymogram and (b), tissue inhibitor of MMP (TIMP) reverse zymogram. Non-ischemic followed by ischaemic samples displayed in matched pairs. Journal of Investigative Dermatology  , DOI: ( /j X x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

6 Figure 5 Pro-matrix metalloproteinase (MMP)-2 levels in the ischemic samples expressed as a percentage of the matched non-ischemic values. There was greater expression of pro-MMP-2 in ischemic samples compared with non-ischemic samples (p<0.001 Wilcoxon's signed-rank test). Journal of Investigative Dermatology  , DOI: ( /j X x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

7 Figure 6 Pro-matrix metalloproteinase (MMP)-2 levels of ischemic, non-ischemic, and controls (varicose vein (VV) and total knee replacement (TKR)) expressed as % of MMP-2 standard. Error bars showing standard error of mean. No statistical difference was found between VV, TKR, and non-ischemic samples (p>0.5, unpaired t test with Welch correction). Comparing; ischemic with non-ischemic, p<0.001 (Wilcoxon's signed-rank test), ischemic and VV, p<0.02, and ischemic with TKR p<0.02 (unpaired t test with Welch correction). Journal of Investigative Dermatology  , DOI: ( /j X x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

8 Figure 7 Active matrix metalloproteinase (MMP)-2 levels in the ischemic samples expressed as a percentage of the matched non-ischemic values. Higher levels of active MMP-2 were detected in the ischemic compared with non-ischemic samples (p<0.001 Wilcoxon's signed-rank test). Journal of Investigative Dermatology  , DOI: ( /j X x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

9 Figure 8 Pro-matrix metalloproteinase (MMP)-2 levels of ischemic, non-ischemic, and controls (varicose vein (VV) and total knee replacement (TKR)) expressed as % of MMP-2 standard. Error bars showing standard error of mean. No statistical difference was found between VV, TKR, and non-ischemic samples (p>0.5 unpaired t test with Welch correction). Comparing; ischemic with non-ischemic, p<0.001 (Wilcoxon's signed-rank test), ischemic and VV, p<0.005, and ischemic with TKR p<0.05 (unpaired t test with Welch correction). Journal of Investigative Dermatology  , DOI: ( /j X x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

10 Figure 9 Tissue inhibitor of MMP (TIMP) levels in ischemic and non-ischemic skin. There was greater expression of TIMP-2 in ischemic compared with non-ishemic skin (a) in individual ischemic samples expressed as a percentage of the matched non-ischemic values (p<0.001 Wilcoxon's signed-rank test), and (b) grouped non-ischemic compared with ischemic skin expressed as % of TIMP-2 standard. Error bars showing standard error of mean (p<0.001 Wilcoxon's signed-rank test). Journal of Investigative Dermatology  , DOI: ( /j X x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

11 Figure 10 Pro-matrix metalloproteinase (MMP)-1 levels in ischemic and non-ischemic skin. There was greater expression of Pro-MMP-1 in ischemic compared with non-ischemic skin, as determined by western blotting (p<0.01, Wilcoxon's signed-rank test). Journal of Investigative Dermatology  , DOI: ( /j X x) Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

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