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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.

References

This article includes 66 references
  1. Goveia J, Stapor P, Carmeliet P. Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease.. EMBO Mol. Med. 2014;6:1105–1120.
    doi: 10.15252/emmm.201404156pmc: PMC4197858pubmed: 25063693google scholar: lookup
  2. Smith RKW, McIlwraith CW. “One Health” in tendinopathy research: Current concepts.. J. Orthop. Res. 2021;39:1596–1602.
    doi: 10.1002/jor.25035pubmed: 33713481google scholar: lookup
  3. Manivong S, Cullier A, Audigié F, Banquy X, Moldovan F, Demoor M, Roullin VG. New trends for osteoarthritis: Biomaterials, models and modeling.. Drug Discov. Today. 2023;28:103488.
    doi: 10.1016/j.drudis.2023.103488pubmed: 36623796google scholar: lookup
  4. Partridge E, Adam E, Wood C, Parker J, Johnson M, Horohov D, Page A. Residual effects of intra-articular betamethasone and triamcinolone acetonide in an equine acute synovitis model.. Equine Vet. J. 2023;55:905–915.
    doi: 10.1111/evj.13899pubmed: 36397207google scholar: lookup
  5. Lawal TA, Wires ES, Terry NL, Dowling JJ, Todd JJ. Preclinical model systems of ryanodine receptor 1-related myopathies and malignant hyperthermia: A comprehensive scoping review of works published 1990–2019.. Orphanet J. Rare Dis. 2020;15:113.
    doi: 10.1186/s13023-020-01384-xpmc: PMC7204063pubmed: 32381029google scholar: lookup
  6. van der Weyden L, Brenn T, Patton EE, Wood GA, Adams DJ. Spontaneously occurring melanoma in animals and their relevance to human melanoma.. J. Pathol. 2020;252:e5505.
    doi: 10.1002/path.5505pmc: PMC7497193pubmed: 32652526google scholar: lookup
  7. Saljic A, Jespersen T, Buhl R. Anti-arrhythmic investigations in large animal models of atrial fibrillation.. Br. J. Pharmacol. 2022;179:838–858.
    doi: 10.1111/bph.15417pubmed: 33624840google scholar: lookup
  8. Winkler PA, Occelli LM, Petersen-Jones SM. Large Animal Models of Inherited Retinal Degenerations: A Review.. Cells 2020;9:882.
    doi: 10.3390/cells9040882pmc: PMC7226744pubmed: 32260251google scholar: lookup
  9. Tashiro J, Rubio GA, Limper AH, Williams K, Elliot SJ, Ninou I, Aidinis V, Tzouvelekis A, Glassberg MK. Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis.. Front. Med. 2017;4:118.
    doi: 10.3389/fmed.2017.00118pmc: PMC5532376pubmed: 28804709google scholar: lookup
  10. Bullone M, Lavoie JP. The equine asthma model of airway remodeling: From a veterinary to a human perspective.. Cell Tissue Res. 2020;380:223–236.
    doi: 10.1007/s00441-019-03117-4pubmed: 31713728google scholar: lookup
  11. Manfredi JM, Jacob SI, Boger BL, Norton EM. A one-health approach to identifying and mitigating the impact of endocrine disorders on human and equine athletes.. Am. J. Vet. Res. 2022;84:ajvr.22.11.0194.
    doi: 10.2460/ajvr.22.11.0194pubmed: 36563063google scholar: lookup
  12. Hood DM, Amoss MS, Grosenbaugh DA. Equine Laminitis: A Potential Model of Raynaud’s Phenomenon.. Angiology 1990;41:270–277.
    doi: 10.1177/000331979004100403pubmed: 2339825google scholar: lookup
  13. Harman RM, Theoret CL, Van de Walle GR. The Horse as a Model for the Study of Cutaneous Wound Healing.. Adv. Wound Care 2021;10:381–399.
    doi: 10.1089/wound.2018.0883pubmed: 34042536google scholar: lookup
  14. Taguchi T, Lopez MJ. An overview of de novo bone generation in animal models.. J. Orthop. Res. 2021;39:7–21.
    doi: 10.1002/jor.24852pmc: PMC7820991pubmed: 32910496google scholar: lookup
  15. Ribitsch I, Baptista PM, Lange-Consiglio A, Melotti L, Patruno M, Jenner F, Schnabl-Feichter E, Dutton LC, Connolly DJ, van Steenbeek FG. Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do.. Front. Bioeng. Biotechnol. 2020;8:972.
    doi: 10.3389/fbioe.2020.00972pmc: PMC7438731pubmed: 32903631google scholar: lookup
  16. Bukowska J, Szóstek-Mioduchowska AZ, Kopcewicz M, Walendzik K, Machcińska S, Gawrońska-Kozak B. Adipose-Derived Stromal/Stem Cells from Large Animal Models: From Basic to Applied Science.. Stem Cell Rev. Rep. 2021;17:719–738.
    doi: 10.1007/s12015-020-10049-ypmc: PMC8166671pubmed: 33025392google scholar: lookup
  17. Beilby KH, Kneebone E, Roseboom TJ, van Marrewijk IM, Thompson JG, Norman RJ, Robker RL, Mol BWJ, Wang R. Offspring physiology following the use of IVM, IVF and ICSI: A systematic review and meta-analysis of animal studies.. Hum. Reprod. Update. 2023;29:272–290.
    doi: 10.1093/humupd/dmac043pmc: PMC10152177pubmed: 36611003google scholar: lookup
  18. Karagianni AE, Lisowski ZM, Hume DA, Scott Pirie R. The equine mononuclear phagocyte system: The relevance of the horse as a model for understanding human innate immunity.. Equine Vet. J. 2021;53:231–249.
    doi: 10.1111/evj.13341pubmed: 32881079google scholar: lookup
  19. Denham J, McCluskey M, Denham MM, Sellami M, Davie AJ. Epigenetic control of exercise adaptations in the equine athlete: Current evidence and future directions.. Equine Vet. J. 2021;53:431–450.
    doi: 10.1111/evj.13320pubmed: 32671871google scholar: lookup
  20. Potente M, Gerhardt H, Carmeliet P. Basic and Therapeutic Aspects of Angiogenesis.. Cell 2011;146:873–887.
    doi: 10.1016/j.cell.2011.08.039pubmed: 21925313google scholar: lookup
  21. Faulkner A, Purcell R, Hibbert A, Latham S, Thomson S, Hall WL, Wheeler-Jones C, Bishop-Bailey D. A thin layer angiogenesis assay: A modified basement matrix assay for assessment of endothelial cell differentiation.. BMC Cell Biol. 2014;15:41.
    doi: 10.1186/s12860-014-0041-5pmc: PMC4263020pubmed: 25476021google scholar: lookup
  22. Garonna E, Botham KM, Birdsey GM, Randi AM, Gonzalez-Perez RR, Wheeler-Jones CPD. Vascular endothelial growth factor receptor-2 couples cyclo-oxygenase-2 with pro-angiogenic actions of leptin on human endothelial cells.. PLoS ONE 2011;6:e18823.
    doi: 10.1371/journal.pone.0223400pmc: PMC3078934pubmed: 21533119google scholar: lookup
  23. Vara D, Watt JM, Fortunato TM, Mellor H, Burgess M, Wicks K, Mace K, Reeksting SB, Lubben A, Wheeler-Jones CPD. Direct Activation of NADPH Oxidase 2 by 2-Deoxyribose-1-Phosphate Triggers Nuclear Factor Kappa B-Dependent Angiogenesis.. Antioxid. Redox Signal. 2018;28:110–130.
    doi: 10.1089/ars.2016.6869pmc: PMC5725637pubmed: 28793782google scholar: lookup
  24. Lane J, Faulkner A, Finding EJ, Lynam EG, Wheeler-Jones CP. Use of a thin layer assay for assessing the angiogenic potential of endothelial cells in vitro.. .
    pubmed: 35451758
  25. Ferrara N. Vascular Endothelial Growth Factor: Basic Science and Clinical Progress.. Endocr. Rev. 2004;25:581–611.
    doi: 10.1210/er.2003-0027pubmed: 15294883google scholar: lookup
  26. Geng K, Wang J, Liu P, Tian X, Liu H, Wang X, Hu C, Yan H. Electrical stimulation facilitates the angiogenesis of human umbilical vein endothelial cells through MAPK/ERK signaling pathway by stimulating FGF2 secretion.. Am. J. Physiol.-Cell Physiol. 2019;317:C277–C286.
    doi: 10.1152/ajpcell.00474.2018pubmed: 30995109google scholar: lookup
  27. Murakami M, Nguyen LT, Hatanaka K, Schachterle W, Chen PY, Zhuang ZW, Black BL, Simons M. FGF-dependent regulation of VEGF receptor 2 expression in mice.. J. Clin. Investig. 2011;121:2668–2678.
    doi: 10.1172/JCI44762pmc: PMC3223828pubmed: 21633168google scholar: lookup
  28. Pepper MS, Ferrara N, Orci L, Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro.. Biochem. Biophys. Res. Commun. 1992;189:824–831.
    doi: 10.1016/0006-291X(92)92277-5pubmed: 1281999google scholar: lookup
  29. Huang H, Lavoie-Lamoureux A, Lavoie JP. Cholinergic stimulation attenuates the IL-4 induced expression of E-selectin and vascular endothelial growth factor by equine pulmonary artery endothelial cells.. Vet. Immunol. Immunopathol. 2009;132:116–121.
    doi: 10.1016/j.vetimm.2009.05.003pubmed: 19501920google scholar: lookup
  30. Benbarek H, Grülke S, Deby-Dupont G, Deby C, Mathy-Hartert M, Caudron I, Dessy-Doize C, Lamy M, Serteyn D. Cytotoxicity of stimulated equine neutrophils on equine endothelial cells in culture.. Equine Vet. J. 2000;32:327–333.
    doi: 10.2746/042516400777032273pubmed: 10952382google scholar: lookup
  31. Bailey SR, Cunningham FM. Inflammatory mediators induce endothelium-dependent adherence of equine eosinophils to cultured endothelial cells.. J. Vet. Pharmacol. Ther. 2001;24:209–214.
    doi: 10.1046/j.1365-2885.2001.00329.xpubmed: 11442800google scholar: lookup
  32. Johnstone S, Barsova J, Campos I, Frampton AR. Equine herpesvirus type 1 modulates inflammatory host immune response genes in equine endothelial cells.. Vet. Microbiol. 2016;192:52–59.
    doi: 10.1016/j.vetmic.2016.06.012pubmed: 27527764google scholar: lookup
  33. Spiesschaert B, Goldenbogen B, Taferner S, Schade M, Mahmoud M, Klipp E, Osterrieder N, Azab W. Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: A Dynamic In Vitro Model.. J. Virol. 2015;89:11899–11908.
    doi: 10.1128/JVI.01809-15pmc: PMC4645325pubmed: 26378176google scholar: lookup
  34. Chiam R, Smid L, Kydd J, Smith K, Platt A, Davis-Poynter N. Use of polarised equine endothelial cell cultures and an in vitro thrombosis model for potential characterisation of EHV-1 strain variation.. Vet. Microbiol. 2006;113:243–249.
    doi: 10.1016/j.vetmic.2005.11.005pubmed: 16338104google scholar: lookup
  35. Menzies-Gow NJ, Bailey SR, Berhane Y, Brooks AC, Elliott J. Evaluation of the induction of vasoactive mediators from equine digital vein endothelial cells by endotoxin.. Am. J. Vet. Res. 2008;69:349–355.
    doi: 10.2460/ajvr.69.3.349pubmed: 18312133google scholar: lookup
  36. de la Rebière G, Franck T, Deby-Dupont G, Salciccia A, Grulke S, Péters F, Serteyn D. Effects of unfractionated and fractionated heparins on myeloperoxidase activity and interactions with endothelial cells: Possible effects on the pathophysiology of equine laminitis.. Vet. J. 2008;178:62–69.
    doi: 10.1016/j.tvjl.2007.08.033pubmed: 17942351google scholar: lookup
  37. Bussche L, Van de Walle GR. Peripheral Blood-Derived Mesenchymal Stromal Cells Promote Angiogenesis via Paracrine Stimulation of Vascular Endothelial Growth Factor Secretion in the Equine Model.. Stem Cells Transl. Med. 2014;3:1514–1525.
    doi: 10.5966/sctm.2014-0138pmc: PMC4250216pubmed: 25313202google scholar: lookup
  38. Dietze K, Slosarek I, Fuhrmann-Selter T, Hopperdietzel C, Plendl J, Kaessmeyer S. Isolation of equine endothelial cells and life cell angiogenesis assay.. Clin. Hemorheol. Microcirc. 2014;58:127–146.
    doi: 10.3233/CH-141877pubmed: 25227198google scholar: lookup
  39. Lessiak U, Pratscher B, Tichy A, Nell B. Bevacizumab Efficiently Inhibits VEGF-Associated Cellular Processes in Equine Umbilical Vein Endothelial Cells: An In Vitro Characterization.. Vet. Sci. 2023;10:632.
    doi: 10.3390/vetsci10110632pmc: PMC10675369pubmed: 37999456google scholar: lookup
  40. Nowak-Sliwinska P, Alitalo K, Allen E, Anisimov A, Aplin AC, Auerbach R, Augustin HG, Bates DO, van Beijnum JR, Bender RHF. Consensus guidelines for the use and interpretation of angiogenesis assays.. Angiogenesis 2018;21:425–532.
    pmc: PMC6237663pubmed: 29766399
  41. Rieger J, Kaessmeyer S, Al Masri S, Huenigen H, Plendl J. Endothelial cells and angiogenesis in the horse in health and disease—A review.. Anat. Histol. Embryol. 2020;49:656–678.
    doi: 10.1111/ahe.12588pubmed: 32639627google scholar: lookup
  42. Salter MM, Seeto WJ, DeWitt BB, Hashimi SA, Schwartz DD, Lipke EA, Wooldridge AA. Characterization of endothelial colony-forming cells from peripheral blood samples of adult horses.. Am. J. Vet. Res. 2015;76:174–187.
    doi: 10.2460/ajvr.76.2.174pubmed: 25629916google scholar: lookup
  43. Seeto WJ, Tian Y, Winter RL, Caldwell FJ, Wooldridge AA, Lipke EA. Encapsulation of Equine Endothelial Colony Forming Cells in Highly Uniform, Injectable Hydrogel Microspheres for Local Cell Delivery.. Tissue Eng. Part C Methods 2017;23:815–825.
    doi: 10.1089/ten.tec.2017.0233pubmed: 28762895google scholar: lookup
  44. Sharpe AN, Seeto WJ, Winter RL, Zhong Q, Lipke EA, Wooldridge AA. Isolation of endothelial colony-forming cells from blood samples collected from the jugular and cephalic veins of healthy adult horses.. Am. J. Vet. Res. 2016;77:1157–1165.
    doi: 10.2460/ajvr.77.10.1157pubmed: 27668588google scholar: lookup
  45. Winter RL, Seeto WJ, Tian Y, Caldwell FJ, Lipke EA, Wooldridge AA. Growth and function of equine endothelial colony forming cells labeled with semiconductor quantum dots.. BMC Vet. Res. 2018;14:247.
    doi: 10.1186/s12917-018-1572-3pmc: PMC6107939pubmed: 30139355google scholar: lookup
  46. Winter RL, Tian Y, Caldwell FJ, Seeto WJ, Koehler JW, Pascoe DA, Fan S, Gaillard P, Lipke EA, Wooldridge AA. Cell engraftment, vascularization, and inflammation after treatment of equine distal limb wounds with endothelial colony forming cells encapsulated within hydrogel microspheres.. BMC Vet. Res. 2020;16:43.
    doi: 10.1186/s12917-020-2269-ypmc: PMC7001230pubmed: 32019556google scholar: lookup
  47. Reyner CL, Winter RL, Maneval KL, Boone LH, Wooldridge AA. Effect of recombinant equine interleukin-1β on function of equine endothelial colony-forming cells in vitro.. Am. J. Vet. Res. 2021;82:318–325.
    doi: 10.2460/ajvr.82.4.318pubmed: 33764832google scholar: lookup
  48. Finding EJT, Purcell R, Menzies-Gow N, Elliott J, Wheeler-Jones C. Phenotypic and functional characterization of equine endothelial cells.. J. Vet. Intern. Med. 2020;34:2830–2989.
    doi: 10.1111/jvim.15904pmc: PMC7968404pubmed: 33037851google scholar: lookup
  49. Faulkner A, Lynam E, Purcell R, Jones C, Lopez C, Board M, Wagner KD, Wagner N, Carr C. Context-dependent regulation of endothelial cell metabolism: Differential effects of the PPARβ/δ agonist GW0742 and VEGF-A.. Sci. Rep. 2020;10:7849.
    doi: 10.1038/s41598-020-63900-0pmc: PMC7217938pubmed: 32398728google scholar: lookup
  50. Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, Hubbard SR, Schlessinger J. Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors.. Science 1997;276:955–960.
    doi: 10.1126/science.276.5314.955pubmed: 9139660google scholar: lookup
  51. Lamar C.H., Turek J.J., Bottoms G.D., Fessler J.F.. Equine endothelial cells in vitro.. Am. J. Vet. Res. 1986;47:956–958.
    pubmed: 3008614
  52. MacEachern K.E., Smith G.L., Nolan A.M.. Methods for the isolation, culture and characterisation of equine pulmonary artery endothelial cells.. Res. Vet. Sci. 1997;62:147–152.
    doi: 10.1016/S0034-5288(97)90137-5pubmed: 9243714google scholar: lookup
  53. Puchalski S.M., Galuppo L.D., Drew C.P., Wisner E.R.. Use of contrast-enhanced computed tomography to assess angiogenesis in deep digital flexor tendonopathy in a horse.. Vet. Radiol. Ultrasound. 2009;50:292–297.
    doi: 10.1111/j.1740-8261.2009.01536.xpubmed: 19507393google scholar: lookup
  54. Marr N., Zamboulis D.E.E., Werling D., Felder A.A.A., Dudhia J., Pitsillides A.A.A., Thorpe C.T.T.. The tendon interfascicular basement membrane provides a vascular niche for CD146+ cell subpopulations.. Front. Cell Dev. Biol. 2022;10:1094124.
    doi: 10.3389/fcell.2022.1094124pmc: PMC9869387pubmed: 36699014google scholar: lookup
  55. Rieger J., Hopperdietzel C., Kaessmeyer S., Slosarek I., Diecke S., Richardson K., Plendl J.. Human and equine endothelial cells in a life cell imaging scratch assay in vitro.. Clin. Hemorheol. Microcirc. 2018;70:495–509.
    doi: 10.3233/CH-189316pubmed: 30400082google scholar: lookup
  56. Hedges J.F., Demaula C.D., Moore B.D., Mclaughlin B.E., Simon S.I., Maclachlan N.J.. Characterization of equine E-selectin.. Immunology. 2001;103:498–504.
    doi: 10.1046/j.1365-2567.2001.01262.xpmc: PMC1783268pubmed: 11529941google scholar: lookup
  57. Hong S.H., Gang E.J., Jeong J.A., Ahn C., Hwang S.H., Yang I.H., Park H.K., Han H., Kim H.. In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells.. Biochem. Biophys. Res. Commun. 2005;330:1153–1161.
    doi: 10.1016/j.bbrc.2005.03.086pubmed: 15823564google scholar: lookup
  58. Wise L.M., Bodaan C.J., Stuart G.S., Real N.C., Lateef Z., Mercer A.A., Riley C.B., Theoret C.L.. Treatment of limb wounds of horses with orf virus IL-10 and VEGF-E accelerates resolution of exuberant granulation tissue, but does not prevent its development.. PLoS ONE. 2018;13:e0197223.
    doi: 10.1371/journal.pone.0197223pmc: PMC5953458pubmed: 29763436google scholar: lookup
  59. Wang S., Li X., Parra M., Verdin E., Bassel-Duby R., Olson E.N.. Control of endothelial cell proliferation and migration by VEGF signaling to histone deacetylase 7.. Proc. Natl. Acad. Sci. USA. 2008;105:7738–7743.
    doi: 10.1073/pnas.0802857105pmc: PMC2409381pubmed: 18509061google scholar: lookup
  60. Jia T., Jacquet T., Dalonneau F., Coudert P., Vaganay E., Exbrayat-Héritier C., Vollaire J., Josserand V., Ruggiero F., Coll J.-L.. FGF-2 promotes angiogenesis through a SRSF1/SRSF3/SRPK1-dependent axis that controls VEGFR1 splicing in endothelial cells.. BMC Biol. 2021;19:173.
    doi: 10.1186/s12915-021-01103-3pmc: PMC8390225pubmed: 34433435google scholar: lookup
  61. Cross M.J., Claesson-Welsh L.. FGF and VEGF function in angiogenesis: Signalling pathways, biological responses and therapeutic inhibition.. Trends Pharmacol. Sci. 2001;22:201–207.
    doi: 10.1016/S0165-6147(00)01676-Xpubmed: 11282421google scholar: lookup
  62. Bahramsoltani M., De Spiegelaere W., Janczyk P., Hiebl B., Cornillie P., Plendl J.. Quantitation of angiogenesis in vitro induced by VEGF-A and FGF-2 in two different human endothelial cultures—An all-in-one assay.. Clin. Hemorheol. Microcirc. 2010;46:189–202.
    doi: 10.3233/CH-2010-1345pubmed: 21135494google scholar: lookup
  63. Pinto-Bravo P., Rebordão M.R., Amaral A., Fernandes C., Galvão A., Silva E., Pessa-Santos P., Alexandre-Pires G., da Costa R.P.R., Skarzynski D.J.. Microvascularization and Expression of Fibroblast Growth Factor and Vascular Endothelial Growth Factor and Their Receptors in the Mare Oviduct.. Animals. 2021;11:1099.
    doi: 10.3390/ani11041099pmc: PMC8070128pubmed: 33921416google scholar: lookup
  64. Song M., Finley S.D.. Mechanistic characterization of endothelial sprouting mediated by pro-angiogenic signaling.. Microcirculation. 2022;29:e12744.
    doi: 10.1111/micc.12744pmc: PMC9285777pubmed: 34890488google scholar: lookup
  65. Cavallaro U., Tenan M., Castelli V., Perilli A., Maggiano N., Van Meir E.G., Montesano R., Soria M.R., Pepper M.S.. Response of bovine endothelial cells to FGF-2 and VEGF is dependent on their site of origin: Relevance to the regulation of angiogenesis.. J. Cell. Biochem. 2001;82:619–633.
    doi: 10.1002/jcb.1190pubmed: 11500940google scholar: lookup
  66. Asahara T., Bauters C., Zheng L.P., Takeshita S., Bunting S., Ferrara N., Symes J.F., Isner J.M.. Synergistic Effect of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor on Angiogenesis In Vivo.. Circulation. 1995;92:365–371.
    doi: 10.1161/01.CIR.92.9.365pubmed: 7586439google scholar: lookup

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.
    doi: 10.1111/acel.70293pubmed: 41250917google scholar: lookup
  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).
    doi: 10.3390/ijms25168575pubmed: 39201261google scholar: lookup
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