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Home / Equine Research Bank / Inflamm Res / The effect of tumour necrosis factor-α and insulin on equin...
Inflammation research : official journal of the European Histamine Research Society ... [et al.]2014; 63(8); 637-647; doi: 10.1007/s00011-014-0736-2

The effect of tumour necrosis factor-α and insulin on equine digital blood vessel function in vitro.

Abstract: Insulin and inflammatory cytokines may be involved in equine laminitis, which might be associated with digital vascular dysfunction. This study determined the effects of TNF-α and insulin on the endothelial-dependent relaxant responses of equine digital blood vessels and on equine digital vein endothelial cell (EDVEC) cGMP production. Methods: Isolated rings of equine digital arteries (EDAs) and veins (EDVs) were obtained and EDVECs were cultured from horses euthanized at an abattoir. Methods: The effect of incubation with TNF-α (10 ng/ml) and/or insulin (1,000 μIU/ml) for 1.5 h or overnight under hyperoxic and hypoxic conditions on carbachol (endothelium-dependent) induced relaxation was assessed. The time course and concentration dependency of the effect of TNF-α and the effect of insulin (1,000 μIU/ml) on EDVEC cGMP production was determined. Results: Incubation of EDAs overnight with TNF-α under hypoxic conditions resulted in endothelial-dependent vascular dysfunction. EDVs produced a more variable response. TNF-α increased EDVEC cGMP formation in a time- and concentration-dependent manner. Insulin had no significant effects. Conclusions: There is a mismatch between the results obtained from isolated vessel rings and cultured endothelial cells suggesting TNF-α may reduce the biological effect of NO by reducing its bioavailability rather than its formation, leading to endothelial cell dysregulation.
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Publication Date: 2014-04-24 PubMed ID: 24764104DOI: 10.1007/s00011-014-0736-2Google Scholar: Lookup
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research looked into the effects of insulin and tumour necrosis factor-alpha (TNF-α), a protein involved in inflammation, on the functioning of blood vessels in the horse hoof. The results found a negative impact on the vessels when TNF-α was present, suggesting a possible role in the development of a horse disease known as laminitis.

Research Methodology

  • Various portions of equine digital arteries (EDAs) and veins (EDVs) were obtained from horses euthanized at an abattoir.
  • The extracted vessels were then treated with TNF-α and/or insulin for different times under various oxygen conditions.
  • The effect of TNF-α and insulin was assessed on the vasculature dependent relaxation induced by carbachol, a medication that stimulates the parasympathetic nervous system.
  • The study also determined the time course and concentration dependency of the effect of TNF-α and insulin on equine digital vein endothelial cell (EDVEC) cGMP (a messenger molecule) production.

Research Findings

  • Treatment of equine digital arteries with TNF-α under oxygen-deprived conditions caused a significant vascular dysfunction, which shows TNF-α can negatively affect the normal functioning of the vessels.
  • The study exhibited a more inconsistent response in digital veins.
  • TNF-α was found to augment the formation of EDVEC cGMP in a time- and concentration-dependent way.
  • Contrary to TNF-α, insulin had no appreciable impact on EDVEC cGMP production.

Conclusions

  • There was a difference between the results obtained from the experiments using detached vessel rings and the cultured endothelial cells.
  • This discrepancy indicates that TNF-α may decrease the biological effect of a molecule called Nitric Oxide (NO) by lowering its availability, rather than its formation.
  • This could consequently lead to poor regulation of endothelial cells’ functioning thereby leading to vascular dysfunction, which may play a role in the tendency towards digital laminitis in horses.

Cite This Article

APA
Menzies-Gow NJ, Wray H, Bailey SR, Harris PA, Elliott J. (2014). The effect of tumour necrosis factor-α and insulin on equine digital blood vessel function in vitro. Inflamm Res, 63(8), 637-647. https://doi.org/10.1007/s00011-014-0736-2

Publication

Inflammation research : official journal of the European Histamine Research Society ... [et al.]
ISSN: 1420-908X
NlmUniqueID: 9508160
Country: Switzerland
Language: English
Volume: 63
Issue: 8
Pages: 637-647

Researcher Affiliations

Menzies-Gow, Nicola J
  • Royal Veterinary College, London, UK, nmenziesgow@rvc.ac.uk.
Wray, H
    Bailey, S R
      Harris, P A
        Elliott, J

          MeSH Terms

          • Animals
          • Arteries / drug effects
          • Arteries / physiology
          • Carbachol
          • Cells, Cultured
          • Cyclic GMP / metabolism
          • Endothelial Cells / drug effects
          • Endothelial Cells / metabolism
          • Horses
          • Hyperoxia / physiopathology
          • Hypoxia / physiopathology
          • In Vitro Techniques
          • Insulin / pharmacology
          • Metatarsophalangeal Joint
          • Tumor Necrosis Factor-alpha / pharmacology
          • Vasodilation / drug effects
          • Veins / drug effects
          • Veins / physiology

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          Citations

          This article has been cited 2 times.
          1. Zamith Cunha R, Gobbo F, Morini M, Salamanca G, Zanoni A, Bernardini C, Gramenzi A, Chiocchetti R. Cannabinoid and cannabinoid related receptors in fibroblasts, inflammatory and endothelial cells of the equine hoof with and without laminitis: novel pharmacological target. Front Vet Sci 2025;12:1723160.
            doi: 10.3389/fvets.2025.1723160pubmed: 41394912google scholar: lookup
          2. Hobbs KJ, Bayless R, Sheats MK. A Comparative Review of Cytokines and Cytokine Targeting in Sepsis: From Humans to Horses. Cells 2024 Sep 5;13(17).
            doi: 10.3390/cells13171489pubmed: 39273060google scholar: lookup
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