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European Journal of Vascular and Endovascular Surgery
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License: Elsevier Non-Commercial
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European Journal of Vascular and Endovascular Surgery
Article . 2006
License: Elsevier Non-Commercial
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European Journal of Vascular and Endovascular Surgery
Article . 2006 . Peer-reviewed
License: Elsevier Non-Commercial
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The Impact of Differential Expression of Extracellular Matrix Metalloproteinase Inducer, Matrix Metalloproteinase-2, Tissue Inhibitor of Matrix Metalloproteinase-2 and PDGF-AA on the Chronicity of Venous Leg Ulcers

Authors: Mwaura, B.; Mahendran, B.; Hynes, N.; Defreitas, D.; Avalos, G.; Adegbola, T.; Adham, M.; +2 Authors

The Impact of Differential Expression of Extracellular Matrix Metalloproteinase Inducer, Matrix Metalloproteinase-2, Tissue Inhibitor of Matrix Metalloproteinase-2 and PDGF-AA on the Chronicity of Venous Leg Ulcers

Abstract

Introduction. Alteration in the expression of extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase-2 (MMP-2), tissue inhibitors of matrix metalloproteinases (TIMP-2) and platelet derived growth factor (PDGF-AA) may contribute to poor healing in venous leg ulcers. Aim. The aim of this study is to determine the expression of EMMPRIN, MMP-2, TIMP-2 and PDGF-AA in the ulcer exudates and perivascular tissue of healing and non-healing chronic venous ulcers. Patients, materials and methods. Forty patients with chronic venous ulcers were included in this study, with a mean age of 60 years. Eleven patients were males and 29 were females. All patients had normal ankle brachial index and a venous ulcer of at least 8 weeks duration. Immuno-histochemistry using monoclonal antibodies to PDGF-AA, MMP-2, TIMP-2 and EMMPRIN was carried out on paraffin embedded punch biopsy skin specimens from the ulcer edge. Enzyme linked immunosorbent assay for PDGF, MMP2 and TIMP-2 were carried out on wound fluids collected from patients. The ulcer size and character at the initial assessment and after 8 weeks were assessed to determine the status of ulcer healing. Results. No significant difference was seen in the expression of TIMP-2, MMP-2 and EMMPRIN between the two groups. However, in the non-healing group high levels of MMP-2 and low levels of TIMP-2 in the wound fluid suggest a strong correlation of these two markers in the state of healing. Analysis of wound fluid by ELISA demonstrated high PDGF-AA in the healing group (p = 0.021). Significantly increased levels of PDGF-AA (p < 0001) was noted in the perivascular area on immuno-histochemistry of healing ulcers. These data suggest that PDGF-AA plays an important role in healing of venous ulcers. Conclusion. Non-healing venous ulcers are associated with greater activity MMP-2 activity. The ratio of MMPs to their inhibitors TIMPs, dictate the rate of healing of the ulcers. PDGF-AA activity is associated with ulcer healing, though the mechanism is unclear. EMMPRIN expression in chronic venous ulcers probably parallels the chronicity of the condition rather than propagate it. However, further studies with larger samples are needed.

Country
Ireland
Keywords

Male, collagen, receptors, Enzyme-Linked Immunosorbent Assay, elevated expression, tissue inhibitors of matrix metalloproteinases, growth-factor, matrix metalloproteinase-2, stimulation, Varicose Ulcer, Matrix metalloproteinase inducer, Humans, Tissue inhibitors of matrix metalloproteinases, lipodermatosclerosis, Medicine(all), Platelet-Derived Growth Factor, Externally hosted open access publications with University of Galway authors, Tissue Inhibitor of Metalloproteinase-2, Platelet derived growth factor, wound fluid, Immunohistochemistry, matrix metalloproteinase inducer, venous ulcer, ulceration, Matrix metalloproteinase-2, Chronic Disease, platelets, Basigin, Matrix Metalloproteinase 2, cells, Venous ulcer, Female, platelet derived growth factor

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    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
99
Top 10%
Top 10%
Top 10%
hybrid