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Endothelial cell hypertrophy is associated with microvascular occlusion in horse wounds.

Abstract: Wound repair in horse limbs is often complicated by excessive fibroplasia and scarring. Occlusion of the microvessels populating the granulation tissue appears to be involved in the excessive accumulation of extracellular matrix during the repair of limb wounds. This study aimed to determine whether endothelial cell hypertrophy or hyperplasia, or both, contribute to microvascular occlusion and whether the pericyte is involved in this anomaly. We created 5 wounds, each 2.5 x 2.5 cm, on both forelimbs and on the body of 6 horses. One limb was bandaged to stimulate excessive wound fibroplasia. Weekly biopsy specimens were evaluated by transmission electron microscopy to measure microvessel luminal diameters and the surface area of endothelial cells and to count endothelial cells and pericytes. Microvessels were occluded significantly more often in limb wounds than in body wounds. The surface area of endothelial cells lining occluded microvessels (mean +/- standard error, 28.4013 +/- 1.5154 microm2) was significantly greater (P = 0.05) than that of cells lining patent microvessels (26.2220 +/- 1.5268 microm2). Conversely, neither the number of endothelial cells nor the number of pericytes differed between patent and occluded microvessels or between limb and body wounds. Furthermore, the wound location and the status of the microvessels (patent or occluded) did not alter the ratio of endothelial cells to pericytes. These data suggest that endothelial cell hypertrophy might play a role in the microvascular occlusion present in granulation tissue of limb wounds in horses, but the contribution of the pericyte remains obscure. La guérison de plaies appendiculaires chez le cheval est souvent compliquée par une fibroplasie abondante menant à une cicatrisation exagérée. Il appert qu’une occlusion des microvaisseaux peuplant le tissu de granulation soit liée à cette accumulation excessive de matrice extracellulaire. La présente étude visait à déterminer si une hypertrophie ou une hyperplasie des cellules endothéliales contribuait à l’occlusion microvasculaire, et si le péricyte participait à cette anomalie. Cinq plaies, mesurant 2.5 × 2.5 cm, ont été créées sur chacun des membres thoraciques ainsi que sur l’aspect latéral de la cage thoracique de 6 chevaux. Un membre fut mis sous bandage afin de stimuler la fibroplasie excessive. Des échantillons de bord de plaies furent prélevés à chaque semaine, pendant 6 semaines, et préparés pour la microscopie électronique par transmission. Le diamètre de la lumière des microvaisseaux ainsi que l’aire des cellules endothéliales furent mesurés, puis le nombre de cellules endothéliales et de péricytes fut déterminé. Les microvaisseaux présents dans les plaies appendiculaires étaient occlus significativement plus souvent que ceux de plaies corporelles. L’aire des cellules endothéliales tapissant ces microvaisseaux occlus (28.4013 ± 1.5154 μm2) était significativement plus grande (P = 0.05) que celle de cellules tapissant les microvaisseaux patents (26.2220 ± 1.5268 μm2). À l’inverse, le nombre de cellules endothéliales et de péricytes était semblable dans les microvaisseaux occlus et patents ainsi que dans les plaies appendiculaires et corporelles. De plus, ni l’emplacement de la plaie ni le statut des microvaisseaux n’altéraient le ratio cellules endothéliales:péricytes. Ces données suggèrent qu’une hypertrophie des cellules endothéliales contribue à l’occlusion microvasculaire présente au niveau du tissu de granulation de plaies appendiculaires chez le cheval, alors que le rôle du péricyte demeure obscur. (Traduit par les auteurs)
Publication Date: 2006-07-21 PubMed ID: 16850943PubMed Central: PMC1477938
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study focused on wound healing in horses and the role of endothelial cells and pericytes in causing microvascular occlusion. The results suggest that the enlargement of endothelial cells may contribute to the blockage of tiny blood vessels in wounded horse limbs, but the role of pericytes is still unclear.

Study Context and Purpose

  • The researchers were studying the process of wound healing in horse limbs, a situation often complicated by excessive fibroplasia and scarring.
  • The blockage or occlusion of tiny blood vessels, known as microvessels, seems to play a role in this excessive accumulation of extracellular matrix.
  • The purpose of this study was to determine whether the enlargement (hypertrophy) or over-multiplication (hyperplasia) of endothelial cells, or even both, contribute to such microvascular occlusion. The researchers also aimed to investigate the role that pericytes play in this problem.

Methodology

  • The researchers created multiple wounds of the same size on the forelimbs and body of six horses. One limb in each horse was bandaged to stimulate excessive wound fibroplasia.
  • Biopsy samples were taken weekly and analysed using transmission electron microscopy. This was to measure microvessel luminal diameters and the surface area of endothelial cells, and to count endothelial cells and pericytes.

Key Findings

  • The study found a significantly higher frequency of microvessel occlusion in limb wounds than in body wounds.
  • The surface area of endothelial cells lining blocked microvessels was significantly larger than those lining open (patent) microvessels.
  • However, there was no significant difference in the number of endothelial cells or the number of pericytes between open and blocked microvessels or between limb and body wounds.
  • No matter the wound location or the microvessel status (open or blocked), the ratio between endothelial cells to pericytes did not change.

Implications

  • The findings suggest a potential role of endothelial cell hypertrophy in the microvascular occlusion in horse limb wounds. This enlarging of endothelial cells might be contributing to the blockages in the tiny blood vessels within the granulation tissues of the wounds.
  • The role of pericytes, however, still remained unclear. There were no significant changes in pericyte number in blocked compared to open vessels, or between different wound locations, indicating that the connection between pericytes and microvascular occlusion needs further study.

Cite This Article

APA
Dubuc V, Lepault E, Theoret CL. (2006). Endothelial cell hypertrophy is associated with microvascular occlusion in horse wounds. Can J Vet Res, 70(3), 206-210.

Publication

ISSN: 0830-9000
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 70
Issue: 3
Pages: 206-210

Researcher Affiliations

Dubuc, Valérie
  • Département de biomédecine vétérinaire, Faculté de médecine vétérinaire, Université de Montréal, Québec.
Lepault, Elodie
    Theoret, Christine L

      MeSH Terms

      • Animals
      • Bandages / veterinary
      • Cicatrix / pathology
      • Cicatrix / veterinary
      • Endothelial Cells / pathology
      • Endothelial Cells / ultrastructure
      • Extremities
      • Female
      • Granulation Tissue / blood supply
      • Granulation Tissue / pathology
      • Granulation Tissue / ultrastructure
      • Horses
      • Hypertrophy / pathology
      • Hypertrophy / veterinary
      • Microcirculation / pathology
      • Microcirculation / ultrastructure
      • Microscopy, Electron, Transmission / veterinary
      • Wound Healing / physiology
      • Wounds and Injuries / pathology
      • Wounds and Injuries / veterinary

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      Citations

      This article has been cited 3 times.
      1. Partusch L, Rutland CS, Martens A, Du Cheyne C, De Spiegelaere W, Michler JK. Collagen composition in equine exuberant granulation tissue reflects tissue immaturity. PLoS One 2025;20(11):e0335179.
        doi: 10.1371/journal.pone.0335179pubmed: 41196884google scholar: lookup
      2. Wise LM, Bodaan CJ, Stuart GS, Real NC, Lateef Z, Mercer AA, Riley CB, Theoret CL. 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(5):e0197223.
        doi: 10.1371/journal.pone.0197223pubmed: 29763436google scholar: lookup
      3. Textor JA, Clark KC, Walker NJ, Aristizobal FA, Kol A, LeJeune SS, Bledsoe A, Davidyan A, Gray SN, Bohannon-Worsley LK, Woolard KD, Borjesson DL. Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses. Stem Cells Transl Med 2018 Jan;7(1):98-108.
        doi: 10.1002/sctm.17-0071pubmed: 29063737google scholar: lookup