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Home / Equine Research Bank / Int J Mol Sci / Equine Endothelial Cells Show Pro-Angiogenic Behaviours in R...
International journal of molecular sciences2024; 25(11); 6017; doi: 10.3390/ijms25116017

Equine Endothelial Cells Show Pro-Angiogenic Behaviours in Response to Fibroblast Growth Factor 2 but Not Vascular Endothelial Growth Factor A.

Abstract: Understanding the factors which control endothelial cell (EC) function and angiogenesis is crucial for developing the horse as a disease model, but equine ECs remain poorly studied. In this study, we have optimised methods for the isolation and culture of equine aortic endothelial cells (EAoECs) and characterised their angiogenic functions in vitro. Mechanical dissociation, followed by magnetic purification using an anti-VE-cadherin antibody, resulted in EC-enriched cultures suitable for further study. Fibroblast growth factor 2 (FGF2) increased the EAoEC proliferation rate and stimulated scratch wound closure and tube formation by EAoECs on the extracellular matrix. Pharmacological inhibitors of FGF receptor 1 (FGFR1) (SU5402) or mitogen-activated protein kinase (MEK) (PD184352) blocked FGF2-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and functional responses, suggesting that these are dependent on FGFR1/MEK-ERK signalling. In marked contrast, vascular endothelial growth factor-A (VEGF-A) had no effect on EAoEC proliferation, migration, or tubulogenesis and did not promote ERK1/2 phosphorylation, indicating a lack of sensitivity to this classical pro-angiogenic growth factor. Gene expression analysis showed that unlike human ECs, FGFR1 is expressed by EAoECs at a much higher level than both VEGF receptor (VEGFR)1 and VEGFR2. These results suggest a predominant role for FGF2 versus VEGF-A in controlling the angiogenic functions of equine ECs. Collectively, our novel data provide a sound basis for studying angiogenic processes in horses and lay the foundations for comparative studies of EC biology in horses versus humans.
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Publication Date: 2024-05-30 PubMed ID: 38892205PubMed Central: PMC11172845DOI: 10.3390/ijms25116017Google Scholar: Lookup
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  • Journal Article

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.

Overview

  • This study focused on isolating and culturing endothelial cells from horse aortas and examined how these cells respond to two growth factors, FGF2 and VEGF-A, that usually influence blood vessel formation.
  • The key finding was that horse endothelial cells respond strongly to FGF2 with pro-angiogenic behaviors, but surprisingly do not respond to VEGF-A, which is typically a classical stimulator of angiogenesis in other species.

Introduction and Context

  • Angiogenesis, the formation of new blood vessels, is critical for health and disease, and is regulated by endothelial cells (ECs) lining blood vessels.
  • Studying angiogenesis in horses is important both for equine health and for using the horse as a model organism for human disease.
  • However, equine endothelial cells are not well studied, particularly in terms of their responses to key growth factors such as FGF2 (Fibroblast Growth Factor 2) and VEGF-A (Vascular Endothelial Growth Factor A).

Methods: Isolation and Culture of Equine Endothelial Cells

  • Endothelial cells were isolated from horse aortas using mechanical dissociation, which physically separates cells from the aorta tissue.
  • To enrich the endothelial cell population, magnetic purification was performed using an antibody that targets VE-cadherin, a molecule specific to endothelial cells.
  • This approach produced enriched cultures of equine aortic endothelial cells (EAoECs) suitable for in vitro experiments on angiogenic behavior.

Key Experimental Findings on Growth Factor Responses

  • Fibroblast Growth Factor 2 (FGF2):
    • Increased proliferation rates of EAoECs, meaning cells divided faster in its presence.
    • Stimulated migration as shown by ‘scratch wound closure’ assays, indicating enhanced ability to move and cover gaps.
    • Promoted tube formation on extracellular matrix, a hallmark of angiogenesis where endothelial cells organize into capillary-like structures.
    • FGF2-induced effects were dependent on signaling pathways involving FGFR1 (FGF receptor 1) and MEK-ERK (mitogen-activated protein kinase pathway), as inhibitors SU5402 (FGFR1 inhibitor) and PD184352 (MEK inhibitor) blocked these responses and the phosphorylation of ERK1/2 proteins.
  • Vascular Endothelial Growth Factor A (VEGF-A):
    • Unlike in many species, VEGF-A had no significant effect on the proliferation, migration, or tube formation of EAoECs.
    • VEGF-A did not trigger phosphorylation of ERK1/2, suggesting a failure to activate typical intracellular signaling cascades in equine endothelial cells.

Gene Expression Findings

  • Gene analysis showed that equine endothelial cells express FGFR1 at much higher levels compared to VEGF receptors VEGFR1 and VEGFR2.
  • This contrasts with human endothelial cells, where VEGF receptors are more prominent and central to controlling angiogenesis.
  • The receptor expression profile helps explain the functional responses observed: horse cells respond mainly to FGF2 and not VEGF-A.

Significance and Implications

  • This research identifies a species-specific difference in how equine endothelial cells regulate angiogenesis, relying predominantly on FGF2 rather than the classical VEGF-A pathway.
  • The findings provide important methodological advances, including optimized isolation and culture techniques, enabling further studies of angiogenesis in horses.
  • Understanding these differences is crucial for developing the horse as a disease model and may help in comparative biology studies to better understand endothelial function across species.
  • This could impact veterinary medicine and potentially inform translational research where horses serve as comparative models for human vascular diseases.

Cite This Article

APA
Finding EJT, Faulkner A, Nash L, Wheeler-Jones CPD. (2024). Equine Endothelial Cells Show Pro-Angiogenic Behaviours in Response to Fibroblast Growth Factor 2 but Not Vascular Endothelial Growth Factor A. Int J Mol Sci, 25(11), 6017. https://doi.org/10.3390/ijms25116017

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 25
Issue: 11
PII: 6017

Researcher Affiliations

Finding, Elizabeth J T
  • Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
Faulkner, Ashton
  • Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
Nash, Lilly
  • Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
Wheeler-Jones, Caroline P D
  • Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.

MeSH Terms

  • Animals
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Horses
  • Endothelial Cells / metabolism
  • Endothelial Cells / drug effects
  • Neovascularization, Physiologic / drug effects
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology
  • Cell Proliferation / drug effects
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism
  • Cell Movement / drug effects
  • Cells, Cultured
  • MAP Kinase Signaling System / drug effects
  • Phosphorylation / drug effects

Grant Funding

  • EPDF 2017-4 / Horserace Betting Levy Board

Conflict of Interest Statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Citations

This article has been cited 2 times.
  1. Iwasaki N, Llewellyn J, Brown J, Zamboulis DE, Finding EJT, Wheeler-Jones CPD, Thorpe CT. Immunolabelling and Micro-Computed Tomography Revealed Age-Related Alterations in 3D Microvasculature of Tendons.. Aging Cell 2026 Jan;25(1):e70293.
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  2. Korablev AV, Sesorova IS, Sesorov VV, Vavilov PS, Mironov A, Zaitseva AV, Bedyaev EV, Mironov AA. New Interpretations for Sprouting, Intussusception, Ansiform, and Coalescent Types of Angiogenesis.. Int J Mol Sci 2024 Aug 6;25(16).
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