Comparative study on microvascular occlusion and apoptosis in body and limb wounds in the horse.
Abstract: Wound repair in horse limbs is often complicated by exuberant granulation tissue, a condition characterized by excessive fibroplasia and scarring and that resembles hypertrophic scars and keloids in man. The aim of this study was to compare microvascular occlusion and apoptosis in wounds of the limb with those of the body, which heal normally. Five 6.25 cm(2) wounds were created on both forelimbs and on the body of six horses. One limb was bandaged to stimulate excessive fibroplasia. Weekly biopsies were evaluated histologically and immunohistochemically for mutant p53 protein by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling to localize and quantify apoptosis, and by electron microscopy to measure microvessel luminal diameters. Histologic examination revealed protracted inflammation as well as slowed epithelialization and deficient fibroblast orientation in limb wounds, particularly those with excessive fibroplasia. Microvessels were occluded significantly more often in limb wounds, and the balance of apoptotic signals was altered against apoptosis in the former, although this could not be confirmed quantitatively. Data suggest that microvascular occlusion and a dysregulated apoptotic process may be involved in the excessive accumulation of extracellular matrix within limb wounds. This might provide a basis for the development of targeted therapies to prevent and treat excessive fibroplasia and extensive scarring in horses.
Publication Date: 2005-09-24 PubMed ID: 16176461DOI: 10.1111/j.1067-1927.2005.00073.xGoogle Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research focuses on understanding why horses often experience complications in limb wound healing processes due to overactive scar tissue formation. The study compares the role of microvascular blockage and cell death regulation in wounds on the limbs and bodies of horses, to possibly inform the development of specialized treatments for preventing and managing excessive scar tissue formation.
Objective and Methodology
- The aim of the study was to compare microvascular occlusion (blockage of tiny blood vessels) and apoptosis (programmed cell death) in horse wounds on the limb (which often heal with extensive scarring) and those of the body (which heal as expected).
- Researchers created 6.25 cm(2) wounds on the body and both forelimbs of six horses. One forelimb on each horse was bandaged to stimulate an overproduction of scarring tissue known as fibroplasia.
- Biopsies from these wounds were taken weekly and examined using histology (study of microscopic structures in tissues), immunohistochemistry (study of antigen in tissues), and electron microscopy (a high-resolution microscope).
- The examination involved localizing and quantifying apoptosis, measuring microvessel diameters, and checking for the presence of the mutant p53 protein – an important protein in preventing cancer.
Findings
- Inflammation lasted longer, and both wound closure by the epithelium and the alignment of fibroblasts (the cells that produce collagen and other fibres) were slowed in the limb wounds, especially those with excessive fibroplasia.
- Microvessels were more frequently blocked in limb wounds than in body wounds.
- There was also an imbalance in apoptotic signals, leaning against apoptosis in limb wounds, though this couldn’t be quantitatively confirmed.
Implications
- The findings suggest a potential involvement of microvascular occlusion and a disrupted apoptotic process in the excessive accumulation of the extracellular matrix within limb wounds. This overaccumulation can lead to extensive scarring and a delay in healing.
- This study could pave the way for the development of targeted therapies to prevent and treat excessive fibroplasia and extensive scarring in horses.
Cite This Article
APA
Lepault E, Céleste C, Doré M, Martineau D, Theoret CL.
(2005).
Comparative study on microvascular occlusion and apoptosis in body and limb wounds in the horse.
Wound Repair Regen, 13(5), 520-529.
https://doi.org/10.1111/j.1067-1927.2005.00073.x Publication
Researcher Affiliations
- Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, Q, Canada.
MeSH Terms
- Animals
- Apoptosis / physiology
- Cicatrix / physiopathology
- Extremities
- Female
- Granulation Tissue / blood supply
- Granulation Tissue / physiopathology
- Horses
- Microcirculation / physiopathology
- Skin / blood supply
- Skin / injuries
- Skin / physiopathology
- Thoracic Wall
- Wound Healing / physiology
Citations
This article has been cited 17 times.- 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.
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- Ribeiro G, Carvalho L, Borges J, Prazeres J. The Best Protocol to Treat Equine Skin Wounds by Second Intention Healing: A Scoping Review of the Literature. Animals (Basel) 2024 May 18;14(10).
- Charlotte C P, Benoit B, Olivier M L. The effects of a synthetic epidermis spray on secondary intention wound healing in adult horses. PLoS One 2024;19(3):e0299990.
- Brock AK, Chamoun-Emanuelli AM, Howard EA, Huntzinger KD, Lawhon SD, Bryan LK, Cosgriff-Hernandez EM, Cohen ND, Whitfield-Cargile CM. Wound swabs versus biopsies to detect methicillin resistant Staphylococcus aureus in experimental equine wounds. Vet Surg 2022 Nov;51(8):1196-1205.
- Di Francesco P, Cajon P, Desterke C, Perron Lepage MF, Lataillade JJ, Kadri T, Lepage OM. Effect of Allogeneic Oral Mucosa Mesenchymal Stromal Cells on Equine Wound Repair. Vet Med Int 2021;2021:5024905.
- Mund SJK, MacPhee DJ, Campbell J, Honaramooz A, Wobeser B, Barber SM. Macroscopic, Histologic, and Immunomodulatory Response of Limb Wounds Following Intravenous Allogeneic Cord Blood-Derived Multipotent Mesenchymal Stromal Cell Therapy in Horses. Cells 2021 Nov 1;10(11).
- Du Cheyne C, Martens A, De Spiegelaere W. High Numbers of CD163-Positive Macrophages in the Fibrotic Region of Exuberant Granulation Tissue in Horses. Animals (Basel) 2021 Sep 18;11(9).
- Lawless SP, Cohen ND, Lawhon SD, Chamoun-Emanuelli AM, Wu J, Rivera-Vélez A, Weeks BR, Whitfield-Cargile CM. Effect of gallium maltolate on a model of chronic, infected equine distal limb wounds. PLoS One 2020;15(6):e0235006.
- 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 Feb 4;16(1):43.
- Lingzhi Z, Meirong L, Xiaobing F. Biological approaches for hypertrophic scars. Int Wound J 2020 Apr;17(2):405-418.
- 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.
- 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.
- Tracey AK, Alcott CJ, Schleining JA, Safayi S, Zaback PC, Hostetter JM, Reinertson EL. The effects of topical oxygen therapy on equine distal limb dermal wound healing. Can Vet J 2014 Dec;55(12):1146-52.
- Miragliotta V, Ipiña Z, Lefebvre-Lavoie J, Lussier JG, Theoret CL. Equine CTNNB1 and PECAM1 nucleotide structure and expression analyses in an experimental model of normal and pathological wound repair. BMC Physiol 2008 Jan 31;8:1.
- Williams PJ, Kurlak LO, Perkins AC, Budge H, Stephenson T, Keisler D, Symonds ME, Gardner DS. Hypertension and impaired renal function accompany juvenile obesity: the effect of prenatal diet. Kidney Int 2007 Aug;72(3):279-89.
- Dubuc V, Lepault E, Theoret CL. Endothelial cell hypertrophy is associated with microvascular occlusion in horse wounds. Can J Vet Res 2006 Jul;70(3):206-10.
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