Fibrosis in horses refers to the formation of excess fibrous connective tissue as a reparative or reactive process following injury or inflammation. This condition can affect various organs and tissues, including the lungs, liver, and skin, leading to impaired function and structural changes. Fibrosis is characterized by the excessive deposition of extracellular matrix components, such as collagen, which can result in tissue stiffness and scarring. In equine medicine, fibrosis can be associated with chronic conditions such as equine asthma or hepatic disease. This page compiles peer-reviewed research studies and scholarly articles that investigate the mechanisms, diagnosis, and management of fibrosis in horses, offering insights into its impact on equine health and potential therapeutic approaches.
Jasiński T, Zdrojkowski Ł, Ferreira-Dias G, Kautz E, Juszczuk-Kubiak E, Domino M.Endometrosis is a frequently occurring disease decreasing mares' fertility. Thus, it is an important disease of the endometrium associated with epithelial and stromal cell alterations, endometrium gland degeneration and periglandular fibrosis. Multiple degenerative changes are found in uterine mucosa, the endometrium. However, their pathogenesis is not well known. It is thought that nuclear factor-κB (NF-κB), a cell metabolism regulator, and its activation pathways take part in it. The transcription of the profibrotic pathway genes of the NF-κB in fibrotic endometria differed between the fo...
Kendall A, Ekman S, Skiöldebrand E.Nerve growth factor (NGF) is a neurotrophin that has been implicated in pain signaling, apoptosis, inflammation and proliferation. The resultant effects depend on interaction with two different receptors; tyrosine kinase A (TrkA) and p75 . NGF increases in synovial fluid from osteoarthritic joints, and monoclonal antibody therapy is trialed to treat osteoarthritis (OA)-related pain. Investigation of the complex and somewhat contradictory signaling pathways of NGF is conducted in neural research, but has not followed through to orthopaedic studies. The objectives of this study were to compare t...
Anantama NA, Du Cheyne C, Martens A, Roth SP, Burk J, De Spiegelaere W, Michler JK.Exuberant granulation tissue (EGT) is often observed during second intention wound healing in horses. Despite its impact on wound care, the basic mechanisms leading to EGT are still unclear and effective strategies to prevent and/or treat EGT are lacking. The development of EGT is a poorly understood, multifactorial process involving hyperproliferating fibroblasts and malfunctional differentiation of keratinocytes, suboptimal wound contraction, dysfunctional vascularisation, and chronic inflammation. To consolidate and describe basic and clinical research literature on EGT and to identify know...
Neto da Silva AC, Costa AL, Teixeira A, Alpoim-Moreira J, Fernandes C, Fradinho MJ, Rebordão MR, Silva E, Ferreira da Silva J, Bliebernicht M....In older mares, increasing collagen fibers (fibrosis) in the endometrium and oviduct predisposes to sub-fertility and infertility. In this study, (i) gene transcription of collagen (qPCR: COL1A1, COL1A2, COL3A1, COL5A1); (ii) total collagen protein (hydroxyproline); (iii) collagen distribution (Picrosirius red staining; polarized light microscopy); and (iv) microvascular density (Periodic acid-Schiff staining), were evaluated in mares' placenta, and related to mares age, and placenta and neonate weights. Samples were collected from the gravid horn, non-gravid horn, and body of the placenta fro...
Martano M, Altamura G, Power K, Liguori P, Restucci B, Borzacchiello G, Maiolino P.It is well known that δ-bovine papillomaviruses (BPV-1, BPV-2 and BPV-13) are one of the major causative agents of equine sarcoids, the most common equine skin tumors. Different viruses, including papillomaviruses, evolved ingenious strategies to modulate autophagy, a complex process involved in degradation and recycling of old and damaged material. Methods: The aim of this study was to evaluate, by immunohistochemistry (IHC) and Western blot (WB) analysis, the expression of the main related autophagy proteins (Beclin 1, protein light chain 3 (LC3) and P62), in 35 BPV1/2 positive equine sarco...
Bessonnat A, Hélie P, Grimes C, Lavoie JP.There is a remodeling of the central airways in horses with severe asthma but whether a similar process occurs in horses with the mild or moderate asthma (MMA) is unknown. Objective: To evaluate lesions affecting the central airways of horses with MMA. Methods: Twelve horses with MMA and 8 control horses. Methods: Case-control retrospective study of horses classified as MMA affected or controls based on history and bronchoalveolar lavage fluid cytology. Endobronchial biopsies were analyzed using histomorphometry and a semiquantitative histologic scoring system. Results: Histomorphometry identi...
Elshalofy A, Wagener K, Weber K, Blanco M, Bauersachs S, Bollwein H.This study aimed to investigate the susceptibility to persistent breeding-induced endometritis (PBIE). Cytobrush samples were collected from 81 broodmares 1-3 days before artificial insemination (AI). Susceptibility to PBIE was evaluated by the presence of ≥ 2 cm of intrauterine fluid 24 h after AI, besides the fertility was determined by a sonographic pregnancy diagnosis 2 weeks after ovulation. RNA expressions were compared between susceptible non-pregnant (SNP) mares (n=9) and resistant pregnant (RP) mares (n=9) as well as between susceptible pregnant (SP) mares (n=9) and susceptible non-...
Doll CU, Niebert S, Burk J.Tendon lesions are common sporting injuries in humans and horses alike. The healing process of acute tendon lesions frequently results in fibrosis and chronic disease. In horses, local mesenchymal stromal cell (MSC) injection is an accepted therapeutic strategy with positive influence on acute lesions. Concerning the use of MSCs in chronic tendon disease, data are scarce but suggest less therapeutic benefit. However, it has been shown that MSCs can have a positive effect on fibrotic tissue. Therefore, we aimed to elucidate the interplay of MSCs and healthy or chronically diseased tendon matrix...
Jasiński T, Zdrojkowski Ł, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Domino M.Endometrosis is an important mares' disease which considerably decreases their fertility. As classic endometrial classification methods might be insufficient for tissue pathological evaluation, further categorization into active/inactive and destructive/non-destructive types was developed by Hoffmann and others. This study aimed to compare NF-κB pathway genes transcription among histopathological types of endometrosis, following Hoffmann and co-authors' classification. Endometrial samples, collected postmortem from cyclic mares ( = 100) in estrus or diestrus, were classified histologically an...
Amaral A, Fernandes C, Szóstek-Mioduchowska A, Lukasik K, Rebordão MR, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G.Cathepsin G (CAT) is a protease released by neutrophils when forming neutrophil extracellular traps that was already associated with inducing type I collagen (COL1) in equine endometrium in vitro. Endometrosis is a fibrotic condition mainly characterized by COL1 deposition in the equine endometrium. The objective was to evaluate if noscapine (an alkaloid for cough treatment with anti-neoplastic and anti-fibrotic properties) would reduce transcription (evaluated by qPCR) and COL1 protein relative abundance (evaluated by western blot) induced by CAT in equine endometrial explants from follicula...
Souza SS, Aguiar FLN, Alves BG, Alves KA, Brandão FAS, Brito DCC, Raposo RDS, Gastal MO, Rodrigues APR, Figueiredo JR, Teixeira DÍA, Gastal EL.Ovarian tissue transplantation methods using cooled and cryopreserved samples have been attractive options for fertility preservation in animal models and humans. The aim of this study was to evaluate the impact of previous exposure to cooling, cryopreservation, and VEGF on the overall efficiency of equine ovarian tissue after heterotopic xenotransplantation in mice. The end points evaluated were follicular morphology and development, follicular and stromal cell densities, angiogenesis (i.e. the density of new and mature blood vessels), collagen types I and III fiber densities, and total fibro...
Du Cheyne C, Martens A, De Spiegelaere W.Exuberant granulation tissue (EGT) is a frequently encountered complication during second intention healing in equine distal limb wounds. Although it is still unknown what exactly triggers the formation of this tissue, previous research has revealed a persistent inflammatory response in these wounds. In this preliminary study we examined this inflammatory response in EGT-developing wounds as well as in experimental induced wounds. Immunohistological stainings were performed to detect primary inflammatory immune cells (MAC387 staining) as well as pro-resolution immune cells (CD163 staining). Ou...
Barton AK, Gehlen H.The term remodeling describes the process resulting in a tissue that is structurally and architecturally altered compared to its healthy counterpart. At least in severe equine asthma, this occurs mainly, but not exclusively, as a consequence of neutrophilic airway inflammation and is characterized by hypertrophy of the smooth muscle layers in airway and arterial walls as well as fibrosis of the bronchial walls and pulmonary interstitial tissue. To date, much less is known for mild to moderate equine asthma. For a long time it was assumed that these processes are irreversible, and at least for ...
Delvescovo B, Tomlinson J, DeNotta S, Hodge E, Bookbinder L, Mohammed HO, Divers TJ.Serum biochemistry results and presence of fibrosis on liver biopsies are frequently used as prognostic indicators in horses with liver dysfunction. The objective of this retrospective multicenter study was to determine if the magnitude of abnormal liver specific biochemical tests such as bile acids (BA), direct bilirubin and gamma-glutamyltransferase (GGT), or the presence of fibrosis reported on liver biopsies was associated with prognosis in horses with liver dysfunction. Eighty-two horses older than one year, examined at four referral hospitals in the eastern United States, with BA values ...
Saljic A, Friederike Fenner M, Winters J, Flethøj M, Eggert Eggertsen C, Carstensen H, Dalgas Nissen S, Melis Hesselkilde E, van Hunnik A....Fibroblasts maintain the extracellular matrix homeostasis and may couple to cardiomyocytes through gap junctions and thereby increase the susceptibility to slow conduction and cardiac arrhythmias, such as atrial fibrillation (AF). In this study, we used an equine model of persistent AF to characterize structural changes and the role of fibroblasts in the development of an arrhythmogenic substrate for AF. Methods: Eleven horses were subjected to atrial tachypacing until self-sustained AF developed and were kept in AF for six weeks. Horses in sinus rhythm (SR) served as control. In terminal open...
McElroy A, Klinge PM, Sledge D, Donahue JE, Glabman RA, Rashmir A.The objectives of this study were to describe the anatomy, histology, and ultrastructure of the equine filum terminale (FT) and to describe the FT in hereditary equine regional dermal asthenia (HERDA), a model of human Ehlers-Danlos syndromes (EDS). Those humans suffer from tethered cord syndrome (TCS) caused by an abnormally structured FT wherein its attachment at the base of the vertebral column leads to long-term stretch-induced injury to the spinal cord. The pathophysiology of TCS in EDS is poorly understood, and there is a need for an animal model of the condition. Histopathologic and ult...
Straticò P, Guerri G, Palozzo A, Di Francesco P, Vignoli M, Varasano V, Petrizzi L.Capsulitis leads to the release of inflammatory mediators in the joint, causing capsular fibrosis and osteoarthritis (OA). Strain elastosonography (SE) measures the elasticity of tissue by evaluating its strain in operator-dependent deformation. The aims of the study were to assess the feasibility, repeatability, and reproducibility of SE for imaging the distal attachment of the joint capsule (DJC) of metacarpophalangeal joints in sound horses (Group S) and in horses with metacarpophalangeal OA (Group P) and to evaluate differences in the elastosonographic patterns of these horses. After a who...
Amaral A, Fernandes C, Szóstek-Mioduchowska A, Rebordão MR, Skarzynski DJ, Ferreira-Dias G.Endometrosis is a reproductive pathology that is responsible for mare infertility. Our recent studies have focused on the involvement of neutrophil extracellular traps enzymes, such as elastase (ELA), in the development of equine endometrosis. Noscapine (NOSC) is an alkaloid derived from poppy opium with anticough, antistroke, anticancer, and antifibrotic properties. The present work investigates the putative inhibitory in vitro effect of NOSC on collagen type I alpha 2 chain () mRNA and COL1 protein relative abundance induced by ELA in endometrial explants of mares in the follicular or mid-lu...
Hurcombe SD, Klein CE, Roessner HA, Engiles JB, Hopster K.To report the use of nylon cable ties (NCT) for omentectomy in the horse. Methods: Experimental study. Methods: Eight healthy adult horses. Methods: Horses underwent nylon cable tie (NCT) ligation of the greater omentum after ventral midline celiotomy. The time required to complete the omentectomy was recorded. Horses were recovered for 14 days before repeat celiotomy, adhesions assessment, and histological examination of the omentectomy site using a proposed histologic grading scheme. The total time for omentectomy procedure and histologic score was assessed for normality. Data are expresse...
Abu-Seida AM, Wafy MN, Hassan EA, Ahmed KA.Ocular neoplasms represent 10% of all equine neoplasms and ocular squamous cell carcinoma (OSCC) is the most common one. This report describes the clinical presentation, laboratory, ultrasonography, postmortem, histopathology and immunohistochemistry findings of a mixed ocular neoplasm in a 10-year-old draft mare. The mare had a one-year history of left ocular mass. Complete destruction of the left eye with loss of vision was observed. A large ulcerated mass oozing blood replaced the left eye. Left parotid lymph node was swollen and had a sinus tract discharging pus. Ultrasonography revealed a...
Collinet A, Grimm P, Julliand S, Julliand V.In horses, abrupt changes from high-fiber (HF) to high-starch (HS) diets can affect the cecal and colonic microbiota. This study investigated modifications and recovery of fecal microbiota after two consecutive abrupt dietary changes. Twelve horses fed HF for 2 weeks were changed to HS for 5 days then returned to HF for 7 weeks. Six received lactic acid bacteria supplementation. Bacterial population diversity, structure, and activity, especially fibrolysis, were assessed to obtain an overview of alteration in hindgut microbiota. Two days after the abrupt change from HF to HS, the findings in f...
Pinto-Bravo P, Rebordão MR, Amaral A, Fernandes C, Galvão A, Silva E, Pessa-Santos P, Alexandre-Pires G, Roberto da Costa RP, Skarzynski DJ....The oviduct presents the ideal conditions for fertilization and early embryonic development. In this study, (i) vascularization pattern; (ii) microvascular density; (iii) transcripts of angiogenic factors (, , ) and their receptors-, , , respectively, and (iv) the relative protein abundance of those receptors were assessed in cyclic mares' oviducts. The oviductal artery, arterioles and their ramifications, viewed by means of vascular injection-corrosion, differed in the infundibulum, ampulla and isthmus. The isthmus, immunostained with CD31, presented the largest vascular area and the highest ...
Amaral A, Fernandes C, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Pinto-Bravo P, Telo da Gama L, Jan Skarzynski D, Ferreira-Dias G.Neutrophils can originate neutrophil extracellular traps (NETs). Myeloperoxidase (MPO) is a peroxidase found in NETs associated to equine endometrosis and can be inhibited by 4-aminobenzoic acid hydrazide (ABAH). Metallopeptidases (MMPs) participate in extracellular matrix stability and fibrosis development. The objectives of this in vitro work were to investigate, in explants of mare's endometrium, (i) the ABAH capacity to inhibit MPO-induced collagen type I (COL1) expression; and (ii) the action of MPO and ABAH on the expression and gelatinolytic activity of MMP-2/-9. Explants retrieved from...
Nottle BF, Tatarniuk DM, Caldwell FJ, Bell CD, Caston SS, Merkatoris PT, Gillen AM, Katzman SA.To describe the presentation, diagnosis, treatment, and outcome for horses with fibro-osseous lesions of the craniofacial complex. Methods: Retrospective multicenter case series. Methods: Thirty horses evaluated for fibro-osseous lesions of the skull from January 1, 2001 through December 31, 2019 in four centers. Methods: Medical records were reviewed for signalment, clinical presentation, histological and diagnostic imaging findings, treatment instituted, and outcome. Long-term outcome information was obtained by owner questionnaire or the medical record. Results: Diagnoses included ossifying...
Bolfa P, Cercone M, Dennis MM, Conan A, Grevemeyer B, Ducharme NG.Equine arytenoid chondritis causes airway obstruction and abnormal upper airway noise due to a space-occupying lesion(s) and decreased abduction. Our objective was to compare clinical scores and ultrasonographic findings with gross and microscopic lesions of naturally occurring arytenoid chondritis, in order to guide surgical treatment. Seventeen naturally affected horses with advanced/severe chronic arytenoid chondritis and 4 control arytenoid cartilages were evaluated after partial arytenoidectomy. Cartilages were sectioned caudal to the corniculate process and the body of each arytenoid was...
Wise LM, Stuart GS, Sriutaisuk K, Adams BR, Riley CB, Theoret CL.Fibroproliferative disorders occur in both humans and horses following skin injury. In horses, wound healing on the limb is often complicated by the formation of fibroproliferative exuberant granulation tissue, characterized by persistent expression of pro-fibrotic transforming growth factor-beta1 (TGF-β1) and deficient expression of anti-inflammatory interleukin-10 (IL-10). IL-10 has been shown to directly modulate fibrotic gene expression in human fibroblasts, so we hypothesized that equine IL-10 (eIL-10) may exert similar anti-fibrotic effects on equine dermal fibroblasts. Cell-lines were ...
Szóstek-Mioduchowska A, Leciejewska N, Zelmańska B, Staszkiewicz-Chodor J, Ferreira-Dias G, Skarzynski D.Equine endometrosis is a chronic degenerative condition, described as endometrial fibrosis that forms in the stroma, under the basement membrane and around the endometrial glands. The role of lysophosphatidic acid (LPA) in the development of tissue fibrosis varies depending on the organ, and its profibrotic role in mare endometrosis remains unclear. The study aimed to establish the endometrial presence of LPA and its receptors (LPAR1-4), together with its effects on connective tissue growth factor (CTGF) and prostaglandins (PG) secretion from equine endometrium under physiological (estrous cyc...
Goto Asakawa M, Mehmood W, Ali M, Oikawa MA.Myocardial atrophy with fibrosis and fatty infiltration involving the cardiac conduction system is relatively unusual in horses. We herein report of such a case in a 13-year-old Arabian broodmare that had spontaneously died on a paddock. An autopsy revealed multifocal myocardial atrophy with concomitant fibrosis and fatty infiltration in both the ventricles and interventricular septum. The Purkinje fibres in the ventricles and interventricular septum were surrounded by thick fibrous or adipose tissues adjacent to atrophic myocardial cells. Myocardial fibrosis and fatty infiltration were likely...
Miró J, Gutiérrez-Reinoso M, da Silva JA, Fernandes C, Rebordão MR, Alexandre-Pires G, Catalán J, Ferreira-Dias G.Collagen fibers and inflammatory cells are the basis for jenny endometrium Kenney and Doig's classification developed for the mare. The infiltration of a large number of eosinophils in the jenny endometrium is intriguing. Eosinophil and fibroblast produced IL33, which has been related to fibrosis development and chronicity. This work on the endometrium consisted of (i) quantification of collagen type I (COL1A2), type III (COL3A1), and IL33 transcripts; (ii) histological localization and quantification of COL1 and COL3 proteins; and (iii) eosinophil and neutrophil count and correlation with col...
Carrillo MF, Kemper D, Woods LW, Carvallo FR.A 22-y-old American Quarter Horse gelding was presented with a history of chronic progressive respiratory problems and a diffuse pulmonary nodular pattern in thoracic radiographs. The horse was euthanized, and 4 formalin-fixed samples of lung were submitted for histopathology. There were multifocal areas of marked thickening of alveolar septa as a result of proliferation of myofibroblasts embedded in fibromyxoid matrix (interpreted as "Masson bodies"), focal areas of fibrosis, and numerous papillary projections of connective tissue into bronchioles. A diagnosis of organizing pneumonia was reac...
Donnelly KS, Giuliano EA, Sharma A, Tandon A, Rodier JT, Mohan RR.To explore (i) the potential of polyethylenimine (PEI) nanoparticles as a vector for delivering genes into equine corneal fibroblasts (ECFs) using green fluorescent protein (GFP) marker gene, (ii) whether PEI nanoparticle-mediated decorin (DCN) gene therapy could be used to inhibit fibrosis in the equine cornea using an in vitro model. Methods: Polyethylenimine-DNA nanoparticles were prepared at nitrogen-to-phosphate (N-P) ratio of 15 by mixing 22 kDa linear PEI and a plasmid encoding either GFP or DCN. ECFs were generated from donor corneas as previously described. Initially, GFP was introduc...
Grimm P, Combes S, Pascal G, Cauquil L, Julliand V.Starchy diets can induce hindgut dysbiosis in horses. The present study evaluated the impact of a yeast (Saccharomyces cerevisiae) and microalgae (Aurantiochytrium limacinum) supplementation on caecal, colonic and faecal microbial ecosystem and on blood inflammatory parameters of horses fed high-fibre or high-starch diets. Six fistulated geldings in a 2 × 2 Latin-square design were alternatively supplemented and received during each period 100 % hay (4 weeks) followed by a 56/44 hay/barley diet (3 weeks). Caecal, colonic and faecal samples were collected 4 h after the morning meal three times...
Yuan Z, Gault EA, Campo MS, Nasir L.Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by localized invasion, rare regression and high recurrence following surgical intervention. Bovine papillomavirus type 1 (BPV-1) and less commonly BPV-2 are now widely recognized as the causative agents of the disease. Fibroblasts isolated from sarcoids are highly invasive. Invasion is associated with a high level of viral gene expression and matrix metalloproteinase upregulation. However, it remains unclear to what extent BPV-1 proteins are involved in the transformation of equine cells. To address this ...
Rebordão MR, Galvão A, Szóstek A, Amaral A, Mateus L, Skarzynski DJ, Ferreira-Dias G.Endometrosis is a degenerative chronic process, characterized by paramount fibrosis development in mare endometrium. This condition is one of the major causes of subfertility/infertility in mares. As in other organs, fibrosis might be a pathologic sequel of many chronic inflammatory diseases. However, aetiology and physiopathologic mechanisms involved in endometrial fibrosis are still controversial. This review presents new hypotheses based on our newest data. As the first line of innate immune defence, systemic neutrophils arrive in the uterus at mating or in the presence of pathogens. A nove...
Barton AK, Gehlen H.Equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) represent a spectrum of chronic inflammatory disease of the airways in horses resembling human asthma in many aspects. Therefore, both are now described as severity grades of equine asthma. Increasing evidence in horses and humans suggests that local pulmonary inflammation is influenced by systemic inflammatory processes and the other way around. Inflammation, coagulation, and fibrinolysis as well as extracellular remodeling show close interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is comm...
Saljic A, Friederike Fenner M, Winters J, Flethøj M, Eggert Eggertsen C, Carstensen H, Dalgas Nissen S, Melis Hesselkilde E, van Hunnik A....Fibroblasts maintain the extracellular matrix homeostasis and may couple to cardiomyocytes through gap junctions and thereby increase the susceptibility to slow conduction and cardiac arrhythmias, such as atrial fibrillation (AF). In this study, we used an equine model of persistent AF to characterize structural changes and the role of fibroblasts in the development of an arrhythmogenic substrate for AF. Methods: Eleven horses were subjected to atrial tachypacing until self-sustained AF developed and were kept in AF for six weeks. Horses in sinus rhythm (SR) served as control. In terminal open...
Van Cleemput J, Poelaert KCK, Laval K, Nauwynck HJ.Equine herpesvirus type 5 (EHV5) is a ubiquitous, yet obscure pathogen in the horse population and is commonly associated with fatal equine multinodular pulmonary fibrosis (EMPF). To date, little is known about the precise pathogenesis of EHV5. Here, we evaluated the dynamics of EHV5 infection in representative ex vivo and in vitro equine models, using immunofluorescence staining and virus titration. EHV5 was unable to infect epithelial cells lining the mucosa of nasal and tracheal explants. Similarly, primary equine respiratory epithelial cells (EREC) were not susceptible to EHV5 following in...
Martins TB, Kommers GD, Trost ME, Inkelmann MA, Fighera RA, Schild AL.Twenty-one cases of pythiosis in horses (n = 10), dogs (n = 9) and cattle (n = 2) were investigated. The aetiology in all cases was confirmed by immunohistochemistry. Data related to the clinical course and outcome and localization of the lesions were obtained from pathology reports. The equine lesions consisted of fibrotic tissue with multiple, often coalescing, areas of immature granulation tissue encircling eosinophilic cores. Affected dogs had gastrointestinal and/or cutaneous lesions with either or both of a granulomatous/pyogranulomatous or necrotizing eosinophilic inflammatory reaction....
Walter I, Handler J, Miller I, Aurich C.Periglandular arrangement of myofibroblasts, associated with the deposition of extracellular matrix (ECM), is a cardinal feature of endometrosis in mares. We hypothesized that a disturbance in the expression of matrix degrading enzymes such as matrix metalloproteinases (MMP's) and matrix cross-linking proteins might lead to an imbalance in deposition and degradation of extracellular matrix components and thereby accentuate degeneration. Therefore, distributions of MMP-2, capable of collagen IV and laminin degradation, and tissue transglutaminase (TG2), a cross-linker of extracellular matrix pr...
Domino M, Jasinski T, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Zabielski R, Sady M, Gajewski Z.Equine endometrosis is a multifactorial chronic degenerative condition, considered to be one of a major causes of equine infertility. The formation of periglandular fibrosis seems to be linked to chronic inflammation of the mare endometrium in a paracrine way and in a response to numerous forms of inflammatory stimuli elicit the net deposition of extracellular matrix (ECM) around the endometrial glands and stroma. We hypothesized some of these stimuli, such as monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and hyaluronan synthases (HASs), may share the nuclear factor-κB (NF...
Kiryu K, Machida N, Kashida Y, Yoshihara T, Amada A, Yamamoto T.Five racehorses in apparently normal condition succumbed to sudden cardiac death (SCD) during or shortly after intensive training exercise. Cardiopathologic examination was performed. In 1 of the 5 horses, the use of an electrocardiogram (ECG) recording taken continuously for 440 sec enabled us to analyze some of the arrhythmias in the terminal event of SCD. The ECG tracing exhibited the R-on-T phenomenon following a pair of ventricular premature contractions (VPCs). The phenomenon rapidly degenerated into ventricular fibrillation, which led to cardiac arrest. In all 5 horses cardiopathologic ...
Arens AM, Barr B, Puchalski SM, Poppenga R, Kulin RM, Anderson J, Stover SM.California horses incur a bone fragility syndrome manifested by pathologic fractures. This study investigated gross, radiographic, and histologic features of the disorder as well as relationships with silicosis and levels of heavy metals and trace minerals through a postmortem study of 9 affected and 3 unaffected horses. Bones and soft tissues were evaluated grossly and histologically. Bones, lymph nodes, and lung tissue were evaluated radiographically. Tissues were evaluated for silicon levels, intracytoplasmic crystals, heavy metals, and trace minerals. All 9 affected horses had osteoporosis...
Szóstek-Mioduchowska A, Słowińska M, Pacewicz J, Skarzynski DJ, Okuda K.Equine endometrial fibrosis (endometrosis) is described as a degenerative chronic condition in the uterus. Its characteristic feature is excessive deposition of extracellular matrix (ECM) components around the endometrial glands and stroma. Although matrix metallopeptidases (MMPs) that mediate ECM turnover are important factors in the process of fibrosis, knowledge of their expression and regulation in endometrosis is limited. In other species, one of the important regulators of MMPs and tissue inhibitors of MMPs (TIMPs) is transforming growth factor (TGF)-β1. The goal of this study was to de...
Finlay M, Yuan Z, Morgan IM, Campo MS, Nasir L.Bovine papillomavirus type 1 infects not only cattle but also equids and is a causative factor in the pathogenesis of commonly occurring equine sarcoid tumours. Whilst treatment of sarcoids is notoriously difficult, cisplatin has been shown to be one of the most effective treatment strategies for sarcoids. In this study we show that in equine fibroblasts, BPV-1 sensitises cells to cisplatin-induced and UVB-induced apoptosis, a known cofactor for papillomavirus associated disease, however BPV-1 transformed fibroblasts show increased clonogenic survival, which may potentially limit the therapeut...
Walter I, Handler J, Reifinger M, Aurich C.Periglandular fibrosis and cystic dilation of uterine glands are associated with equine endometriosis. The presence of extracellular matrix proteins (collagen type I, III and IV, laminin and fibronectin) in healthy and endometriotic specimens was demonstrated by immunohistochemistry. The distribution of collagen I, but not collagen III, was dependent on the stage of the oestrous cycle. The arrangement of collagen I and collagen III in endometriotic specimens was similar to that in normal endometrium. In periglandular fibrosis, collagen IV, laminin and fibronectin deposition outside the basemen...
van der Linde-Sipman JS, Kroneman J, Meulenaar H, Vos JH.Four horses are described with rupture of the aortic arch and pulmonary trunk which resulted in a fistula between these vessels. Ruptures were located near the ligamentum arteriosum. Histological examination of the vessel walls revealed media necrosis which was probably due to intimal thickening and/or medial fibrosis of the vasa vasorum.
Alpoim-Moreira J, Fernandes C, Pimenta J, Bliebernicht M, Rebordão MR, Castelo-Branco P, Szóstek-Mioduchowska A, Skarzynski DJ, Ferreira-Dias G.Endometrium type I (COL1) and III (COL3) collagen accumulation, periglandular fibrosis and mare infertility characterize endometrosis. Metalloproteinase-2 (MMP-2), MMP-9 and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) are involved in collagen turnover. Since epigenetic changes may control fibroproliferative diseases, we hypothesized that epigenetic mechanisms could modulate equine endometrosis. Epigenetic changes can be reversed and therefore extremely promising for therapeutic use. Methylation pattern analysis of a particular gene zone is used to detect epigenetic changes. DNA...
Tremaine WH, Clarke CJ, Dixon PM.Biopsies collected from 79 referred cases of equine sinonasal disease, including 27 horses with primary sinusitis, 10 with secondary dental sinusitis, 19 with sinus cysts, 11 with progressive ethmoid haematomata (PEH), 4 with false nostril epidermal inclusion cysts, 4 with sinonasal polyps, 3 with sinonasal mycosis and from 2 control animals were examined histologically. Observations were made on epithelial type and integrity, cellular inflammatory response, fibroplasia and presence of potential pathogens. Chronic inflammatory changes including mucosal thickening, ulceration and significant fi...
Muylle E, Vandenhende C, Oyaert W, Thoonen H, Vlaeminck K.Thirty-two horses were examined with a history of poor performance and unthriftiness several months after the ingestion of feed containing monensin sodium. Cardiac abnormality was diagnosed in 8 cases and suspected in 4 others. Necropsy examinations were performed on 6 cases with marked clinical symptoms and evidence of circulatory failure was found. Marked cardiac myopathy and fibrosis was a consistent feature. It is concluded that ingestion of monensin sodium by horses may cause either acute death or delayed cardiac circulatory failure as a result of specific cardiac myodegeneration.
Stegelmeier BL, Gardner DR, James LF, Molyneux RJ.Houndstongue (Cynoglossum officinale), a noxious weed that contains pyrrolizidine alkaloids (PAs), infests pastures and fields in the western United States and Europe. The purpose of this study was to develop techniques to better diagnose PA poisoning and describe the progression of gross and microscopic lesions caused by houndstongue intoxication. Six horses were gavaged daily with a suspension of houndstongue containing 5 or 15 mg/kg total PA for 14 days. Two horses were treated similarly with ground alfalfa as controls. Liver biopsy samples and serum biochemical and hematologic values were ...
Jasiński T, Zdrojkowski Ł, Kautz E, Juszczuk-Kubiak E, Ferreira-Dias G, Domino M.Endometrosis is an important mares' disease which considerably decreases their fertility. As classic endometrial classification methods might be insufficient for tissue pathological evaluation, further categorization into active/inactive and destructive/non-destructive types was developed by Hoffmann and others. This study aimed to compare NF-κB pathway genes transcription among histopathological types of endometrosis, following Hoffmann and co-authors' classification. Endometrial samples, collected postmortem from cyclic mares ( = 100) in estrus or diestrus, were classified histologically an...
Sørensen MA, Petersen LJ, Bundgaard L, Toft N, Jacobsen S.As in other fibroproliferative disorders, hypoxia has been suggested to play a key role in the pathogenesis of exuberant granulation tissue (EGT). The purpose of this study was to investigate metabolism and blood flow locally in full-thickness wounds healing with (limb wounds) and without (body wounds) formation of EGT. Microdialysis was used to recover endogenous metabolites from the wounds, and laser Doppler flowmetry was used to measure blood flow. Measurements were performed before wounding and 1-28 days after wounding. Blood flow was consistently lower in limb wounds than in body wounds t...
van Schie HT, Bakker EM, Jonker AM, van Weeren PR.To evaluate effectiveness of computerized discrimination between structure-related and non-structure-related echoes in ultrasonographic images for quantitative evaluation of tendon structural integrity in horses. Methods: 4 superficial digital flexor tendons (2 damaged tendons, 2 normal tendons). Methods: Transverse ultrasonographic images that precisely matched histologic sections were obtained in fixed steps along the long axis of each tendon. Distribution, intensity, and delineation of structure-related echoes, quantitatively expressed as the correlation ratio and steadiness ratio , were co...
Todd FG, Stermitz FR, Schultheis P, Knight AP, Traub-Dargatz J.Horses in a few, localized northern Colorado pastures exhibited weight loss and colic. At post mortem, intestinal fibrosis and vascular sclerosis of the small intestine was identified. The pastures where the affected horses grazed were overrun by field bindweed (Convolvulus arvensis). Bindweed from the pasture was found to contain the tropane alkaloids tropine, pseudotropine, and tropinone and the pyrrolidine alkaloids cuscohygrine and hygrine. Laboratory mice readily ate C. arvensis and exhibited a variety of abnormal clinical signs depending on the amount eaten. Similar alkaloids have been f...
Williams KJ, Robinson NE, Defeijter-Rupp H, Millerick-May M, Stack A, Hauptman J, Derksen FJ.Exercise-induced pulmonary hemorrhage (EIPH), which has been reported in humans and a variety of domestic animals following strenuous exercise, is most often documented in racehorses. Remodeling of pulmonary veins (VR) in equine EIPH was recently described, suggesting that it contributes to the pathogenesis of the disease. The cause of VR is unknown. We tested the hypothesis that the development of VR follows pulmonary blood flow distribution, preferentially occurring in the caudodorsal lung region. Furthermore, we hypothesized that VR underpins development of the other lesions of EIPH patholo...
Szóstek-Mioduchowska AZ, Baclawska A, Rebordão MR, Ferreira-Dias G, Skarzynski DJ.An increasing number of studies have shown that prostaglandins (PGs) exert multiple regulatory actions in the processes associated to tissue remodeling and fibrosis. Extracellular matrix (ECM) turnover is mediated by matrix metallopeptidases (MMPs). The knowledge about the regulation of their expression in mare endometrium is still limited. Thus, the aim of this study was to investigate whether: (i) profibrotic transforming growth factor (TGF)-β1 modulates PG production in equine endometrium; and (ii) PGE and PGF modulate MMPs, their tissue inhibitors (TIMPs), and collagen 1 (COL1) expression...
Young M, Moshood O, Zhang J, Sarbacher CA, Mueller POE, Halper J.Horses afflicted with degenerative suspensory ligament desmitis (DSLD) suffer from progressive leg pain and lameness without history of trauma. DSLD is a systemic disorder caused by abnormal accumulation of proteoglycans in many connective tissues. One proteoglycan found in higher quantities in DSLD is decorin. The accumulated decorin has an abnormally glycosylated glycosaminoglycan chain in DSLD. In addition to acellular accumulations of proteoglycans foci of active fibroblasts/tenoblasts were observed in some tendons and suspensory ligaments (SLs) from DSLD cases We have hypothesized that th...
Miele A, Dhaliwal K, Du Toit N, Murchison JT, Dhaliwal C, Brooks H, Smith SH, Hirani N, Schwarz T, Haslett C, Wallace WA, McGorum BC.Donkey pulmonary fibrosis (DPF) is a spontaneous syndrome of aged donkeys with a high prevalence (35%). No previous detailed characterization of DPF has been performed. We sought to determine the similarities between DPF and recognized patterns of human pulmonary fibrosis. Methods: Whole lungs were collected from 32 aged donkeys at routine necropsy. Gross examination revealed pulmonary fibrosis in 19 donkeys (DPF cases), whereas 13 (control cases) had grossly normal lungs. Eighteen whole inflated ex vivo lungs (11 DPF cases, seven control cases) were imaged with high-resolution CT (HRCT) scan,...
Back H, Kendall A, Grandón R, Ullman K, Treiberg-Berndtsson L, Ståhl K, Pringle J.A standardbred gelding with a history of 10 days pyrexia and lethargy was referred to the Equine Hospital at the Swedish University of Agricultural Sciences in Uppsala, Sweden.The horse had tachypnea with increased respiratory effort and was in thin body condition. Laboratory findings included leukocytosis, hyperfibrinogenemia and hypoxemia. Thoracic radiographs showed signs of pneumonia with a multifocal nodular pattern, which in combination with lung biopsy findings indicated Equine Multinodular Pulmonary Fibrosis (EMPF). EMPF is a recently described disease in adult horses with clinical s...
Durgam SS, Stewart AA, Pondenis HC, Yates AC, Evans RB, Stewart MC.To compare in vitro expansion of equine tendon- and bone marrow-derived cells with fibroblast growth factor-2 (FGF-2) supplementation and sequential matrix synthesis with pulverized tendon and insulin-like growth factor-I (IGF-I). Methods: Cells from 6 young adult horses. Methods: Progenitor cells were expanded in monolayers with FGF-2, followed by culture with autogenous acellular pulverized tendon and IGF-I for 7 days. Initial cell isolation and subsequent monolayer proliferation were assessed. In pulverized tendon cultures, cell viability and expression of collagen types I and III and carti...
