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

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

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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Crossref · 10.1046/j.1523-1747.2000.00036.x

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  • Factors crucial for wound healing are degraded or inactivated by proteolytic cleavage in chronic wounds.

    “As a consequence, factors crucial for wound healing, e.g., the major proteinase inhibitors (e.g., α1-proteinase inhibitor and α2-macroglobulin), components of the provisional wound matrix (e.g., fibronectin and vitronectin), growth factors (e.g., PDGF, VEGF) are degraded or inactivated by proteolytic cleavage in chronic wounds [246, 247].”

    From Transition from inflammation to proliferation: a critical step during wound healing (2016) · cites this paper as [247]

    The Results and Discussion (page unavailable) show that VEGF is cleaved and degraded by proteases in chronic wound fluid. The paper also reports decreased activity of some proteinase inhibitors and cites earlier work on matrix components, but it does not establish proteolytic cleavage of every example in the citing sentence, including PDGF. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • In chronic wounds, there is a marked increase in serine proteases that degrade matrix components including fibronectin and key growth factors required for extracellular matrix remodeling and cell growth.

    “Last, in chronic wounds, there is a marked increase in serine proteases that degrades matrix components, including fibronectin, as well as various key growth factors, all of which are required for remodeling of the ECM and cell growth (38-41).”

    From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [41]

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Citations

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Research works printed but not linked: 4

  1. Dvorak, 1995, VPF/VEGF, microvascular hypermeability, and angiogenesis, Am J Path, 146, 1029
  2. Lei, 1998, Identification and characterization of a new splicing variant of VEGF.VEGF183, Biochem Biophys Acta, 1443, 400
  3. Nissen, 1998, VEGF mediates angiogenic activity during the proliferative phase of wound healing, Am J Path, 152, 1445
  4. Stürzebecher, 1996, 3-Amidinophenylalanine-derivates as inhibitors of enzymes of the fibrinolytic system, Ann Hematol, 72, A33

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Metadata

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
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
Licence
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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