Cited by 349Wound Healing and TreatmentsAngiogenesis and VEGF in CancerLymphatic System and Diseases

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Expression and Proteolysis of Vascular Endothelial Growth Factor is Increased in Chronic Wounds

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Lauer, Gereon, Sollberg, Stephan, Cole, Melanie, Krieg, Thomas, Eming, Sabine A., Flamme, Ingo, Stürzebecher, Jörg, Mann, Karlheinz·2000·Journal of Investigative Dermatology

DOI 10.1046/j.1523-1747.2000.00036.x

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Abstract

Degradation of angiogenic mediators might be an underlying cause of chronic wounds. To test this hypothesis, we evaluated the expression and integrity of vascular endothelial growth factor, a potent angiogenic mediator, and its receptors, Flt-1 and KDR, in chronic venous leg ulcerations. Immunohisto- chemical, in situ hybridization, and semiquantitative reverse transcriptase polymerase chain reaction analyses all indicate that expression of vascular endothelial growth factor is elevated in ulcerative tissue, with vascular endothelial growth factor mRNA being especially pronounced in the hyperplastic epithelium of the wound margin. Flt-1 and KDR protein and mRNA were detected in the papillary vessels in close vicinity to the lesional epithelium of chronic wounds. Although increased expression of vascular endothelial growth factor protein was detected in the epidermis, the intensity of this staining was weak compared with the epidermal staining in psoriatic lesions and compared with the strong vascular endothelial growth factor mRNA signal in chronic wounds and psoriasis. To analyze whether this apparent decrease in immunoreactivity could be the result of degradation of vascular endothelial growth factor by proteolytic activities from the wound environment, we examined the stability of recombinant vascular endothelial growth factor in wound fluid from chronic leg ulcers. As demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, incubation of rVEGF165 with chronic, but not acute, wound fluid resulted in rapid proteolytic degradation of rVEGF165. Protease inhibitor studies indicate that serine proteases, such as plasmin, are involved in this degradation. Together, our data show that, although vascular endothelial growth factor expression is elevated in chronic wounds, increased proteolytic activity in this environment results in its degradation, which may contribute to an impaired wound healing response.

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Authors: Lauer, G., Sollberg, S., Cole, M., Krieg, T., Eming, S. A., Flamme, I., Stürzebecher, J., & Mann, K.
Affiliations: University of Cologne (DE)
Friedrich Schiller University Jena (DE)
Max Planck Institute of Biochemistry (DE)
Corresponding author: Eming, Sabine A.
ORCID: Krieg, Thomas
Eming, Sabine A.
Flamme, Ingo
Mann, Karlheinz
Venue: Journal of Investigative Dermatology
Publisher: Elsevier BV
Published: 2000-07
Volume: 115
Issue: 1
Pages: 12-18
ISSN: 0022-202X (ISSN-L)
DOI: 10.1046/j.1523-1747.2000.00036.x
OpenAlex: W2004127276
Cited by: 349
References: 43
Citations by year: 2026: 3 · 2025: 18 · 2024: 16 · 2023: 11 · 2022: 21 · 2021: 10 · 2020: 17 · 2019: 10 · 2018: 15 · 2017: 13 · 2016: 15 · 2015: 13 · 2014: 13 · 2013: 16 · 2012: 15
FWCI: 11.66
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 5632 d)
Locations: Journal of Investigative Dermatology (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Health Sciences › Medicine › Surgery › Wound Healing and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
Keywords: vascular endothelial growth factor, chronic wounds, chronic venous leg ulcers, proteolysis, VEGF receptors, Flt-1, KDR, serine protease, plasmin, wound fluid, delayed wound healing, psoriasis, angiogenic mediators
MeSH terms: Chronic Disease, Drug Stability, Exudates and Transudates, Fibrinolysin, Humans, Leg Ulcer, Lymphokines, Protease Inhibitors, Proto-Oncogene Proteins, Recombinant Proteins, RNA, Messenger, Wounds and Injuries, Up-Regulation, Gene Expression, Endothelial Growth Factors, Receptors, Growth Factor, Protein Isoforms, Receptor Protein-Tyrosine Kinases, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A

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Expression and Proteolysis of Vascular Endothelial Growth Factor is Increased in Chronic Wounds

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