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.
Lombardi F, Palumbo P, Augello FR, Giusti I, Dolo V, Guerrini L, Cifone MG, Giuliani M, Cinque B.The ability of a collagen-based matrix to support cell proliferation, migration, and infiltration has been reported; however, the direct effect of an aqueous collagen suspension on cell cultures has not been studied yet. In this work, the effects of a high-concentration aqueous suspension of a micronized type I equine collagen (EC-I) have been evaluated on a normal mouse fibroblast cell line. Immunofluorescence analysis showed the ability of EC-I to induce a significant increase of type I and III collagen levels, parallel with overexpression of crucial proteins in collagen biosynthesis, matura...
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...
Read RM, Boys-Smith S, Bathe AP. There is limited information concerning the ultrasonographic appearance of suspensory ligament branches (SLB) in sports horses. Publications exist on clinical injuries that lead to loss of training days and retirement, but not on the appearance of SLBs in high level showjumping Warmbloods. To demonstrate the prevalence of subclinical SLB abnormalities in regularly competing high-level showjumpers; to grade each branch 0-3; compare forelimb vs. hindlimb and medial vs. lateral SLBs; subjectively assess periligamentous fibrosis; measure cross sectional area (CSA) and to gather competition follo...
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...
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...
Combarros D, Wilhelmi-Vilarrasa I, Lacroux C, Semin MO, Delverdier M, Grebert M, Trumel C, Cadiergues MC, Lallemand EA.Mast cell tumor (MCT) has long been considered as an uncommon neoplasm in horses. Cytological and behavioral evidence of its malignancy is usually lacking, and only a few reports have described MCT displaying malignant behavior. An 18-year-old Friesian stallion presented with a one-year history of intermittent and progressive skin lesions on the left forelimb associated with intense, generalized pruritus and apathy temporarily responsive to glucocorticoids and antibiotics. The horse was alert and responsive with poor body condition and marked generalized pruritus. The left forelimb was markedl...
Despite being one of the major causes of infertility in mares, the mechanisms responsible for equine endometrosis are still unclear and controversial. In the last few years, many investigations focused on local immune response modulation. Since it is generally accepted that endometrial fibrosis increases with age, we hypothesize that older mares could show altered local immune modulation, initiating a pro-inflammatory and tissue remodeling cascade of events that could lead to endometrosis. The aim of this study, indeed, is to evaluate and describe the local gene expression of genes involved in...
Abs V, Bonicelli J, Kacza J, Zizzadoro C, Abraham G.Interaction between epithelial cells and fibroblasts play a key role in wound repair and remodelling in the asthmatic airway epithelium. We present the establishment of a co-culture model using primary equine bronchial epithelial cells (EBECs) and equine bronchial fibroblasts (EBFs). EBFs at passage between 4 and 8 were seeded on the bottom of 24-well plates and treated with mitomycin C at 80% confluency. Then, freshly isolated (P0) or passaged (P1) EBECs were seeded on the upper surface of membrane inserts that had been placed inside the EBF-containing well plates and grown first under liquid...
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...
Hesselkilde EZ, Carstensen H, Flethøj M, Fenner M, Kruse DD, Sattler SM, Tfelt-Hansen J, Pehrson S, Braunstein TH, Carlson J, Platonov PG....Large animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model. Nine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrilla...
Alpoim-Moreira J, Fernandes C, Rebordão MR, Amaral A, Pinto-Bravo P, Bliebernicht M, Skarzynski DJ, Ferreira-Dias G.Inflammation and fibroproliferative diseases may be modulated by epigenetic changes. Therefore, we suggest that epigenetic mechanisms could be involved in equine endometrosis pathogenesis. DNA methylation is one of the methods to evaluate epigenetics, through the transcription of methyltransferases (DNMT1, DNMT3A, DNMT3B). The correlation between DNMTs and collagen (COL) transcripts was assessed for the different Kenney and Doig's (Current Therapy in Theriogenology. Philadelphia: WB Saunders; 1986) endometrium categories. Endometrial biopsies were randomly collected from cyclic mares. Histolog...
Elemmawy YM, Senna NA, Abu-Seida AM, Youssef AF.Injury of suspensory ligament (SL) branch is a frequently diagnosed problem in horses of different ages and disciplines. This case reports for the first time the ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) findings in a 10-year-old draught horse with traumatic chronic SL branch desmitis of 8 months duration. The horse had a grade 3 of 5 left hindlimb lameness with a moderately hot, painful, and diffuse swelling from the tarsus till the hoof. Ultrasonography, both SL branches appeared as enlarged hyperechogenic structures with poor demarcation of their margins a...
Szóstek-Mioduchowska AZ, Baclawska A, Okuda K, Skarzynski DJ.Equine endometrosis (endometrial fibrosis) is a degenerative chronic process that occurs in the uterus of the mare and disturbs proper endometrial function. Fibrosis is attributed to excessive deposition of extracellular matrix (ECM) components. The turnover of ECM is mediated by matrix metallopeptidases (MMP). Previously, it was shown that cytokines modulate MMP expression in other tissues and may regulate fibrosis indirectly by attracting inflammatory cells to the site of inflammation and directly on various tissues. However, the regulation of MMP expression in equine endometrosis is still r...
Ochi A, Sekiguchi M, Tsujimura K, Kinoshita T, Ueno T, Katayama Y.Equine multinodular pulmonary fibrosis (EMPF) is a recently described form of interstitial pneumonia associated with equine herpesvirus type 5 (EHV-5). This disease has been reported in North and South America, Europe and Oceania but not, to our knowledge, in horses in Japan. We diagnosed EMPF in two Thoroughbred horses in Japan on the basis of gross and histopathological findings. In both cases, significant gross lesions, restricted to the lungs, consisted of numerous firm and coalescing nodules widely distributed throughout the lung. The nodules were <3 cm in diameter and pale white to t...
Reynolds A, Keen JA, Fordham T, Morgan RA.Obesity is a common feature of equine metabolic syndrome (EMS). In other species, obese adipose tissue shows pathological features such as adipocyte hypertrophy, fibrosis, inflammation and impaired insulin signalling all of which contribute to whole body insulin dysregulation. Such adipose tissue dysfunction has not been investigated in horses. Objective: To determine if obese horses with EMS have adipose tissue dysfunction characterised by adipocyte hypertrophy, fibrosis, inflammation and altered insulin signalling. Methods: Cross-sectional post-mortem study. Methods: Samples of peri-renal (v...
Manso-Díaz G, Jiménez Martínez MLÁ, García-Fernández RA, Herrán R, Santiago I.A 30-year-old Standardbred gelding was referred for chronic pleural effusion. Thoracic ultrasound revealed marked bilateral pleural effusion and a large heterogeneous mass within the cranial mediastinum, which extended from the right 5th to the 11th intercostal space. Subsequently, on thoracic radiographs, the cranial mediastinal mass was confirmed, and a nodular interstitial pattern was identified in the lungs. Because of progressive clinical deterioration of the patient, the owners elected humane euthanasia and necropsy was performed. The mediastinal mass was consistent with an ectopic thyro...
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...
Suarez-Fuentes DG, Tatarniuk DM, Caston SS, Bell CD, Loinaz RJ, Hostetter JM.To evaluate the efficacy and safety of a transendoscopic monopolar electrosurgical triangle-tip knife as instrumentation to perform unilateral ventriculocordectomy (VC) in healthy adult horses. Methods: In vivo experimental study. Methods: Nine horses donated for medical conditions unrelated to respiratory system. Methods: The triangle-tip knife was applied in contact fashion. Left VC was performed under standing sedation. Endoscopic images of the upper airway were graded for inflammation by 2 masked surgeons preoperatively and immediately, 24 hours and, in 2 cases, 7 and 14 days postopera...
Rebordão MR, Amaral A, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G.Prostaglandin E (PGE) has contradictory effects in many organs. It may have proinflammatory, anti-inflammatory, or anti-fibrotic roles, depending on the type of receptors to which it binds. By signaling through its receptors EP2 and EP4, PGE mediates anti-inflammatory and anti-fibrotic actions. In spite of chronic endometrial fibrosis (endometrosis) being a major cause of mare infertility, its pathogenesis is not fully understood. We have shown that contact of mare endometrium in vitro with neutrophil extracellular traps (NETs) proteases favors endometrial collagen type I production. Therefor...
Szóstek-Mioduchowska AZ, Lukasik K, Skarzynski DJ, Okuda K.Transforming growth factor (TGF)-β1 not only regulates cell growth, development, and tissue remodeling, but it also participates in the pathogenesis of tissue fibrosis. In the equine endometrium, the concentration of TGF-β1 is correlated with endometrosis (equine endometrial fibrosis). In other tissues, TGF-β1 induces differentiation of many cell types into myofibroblasts. These cells are characterized by α-smooth muscle actin (α-SMA) expression and an ability to deposit excessive amounts of extracellular matrix (ECM) components. The aim of the study was to determine whether TGF-β1 plays...
Amaral A, Fernandes C, Lukasik K, Szóstek-Mioduchowska A, Baclawska A, Rebordão MR, Aguiar-Silva J, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G.We have shown that bacteria induce neutrophil extracellular traps (NETs) in mare endometrium. Besides killing pathogens, NETs may contribute for endometrosis (chronic endometrium fibrosis). Since elastase (ELA) is a NETs component that regulates fibrosis and prostaglandin (PG) output, the aim was to evaluate if inhibition of ELA would affect collagen 1 (COL1) transcription and PGs secretion by endometrium explants, in different estrous cycle phases. Follicular-FP (n = 8) and mid luteal-MLP (n = 7) phases explants were cultured for 24-48 hr with medium alone (Control), ELA (0.5 μg/ml,1 ...
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...
Easton-Jones CA, Madigan JE, Barnum S, Maxwell LK, Taylor SD, Arnesen T, Pusterla N.Equine herpesvirus-5 is commonly isolated from the lungs of horses with EMPF, suggesting an etiological link. Valacyclovir is used empirically to treat EMPF; however, no data is available concerning its impact on EHV-5 viral kinetics. Objective: To determine the effect of oral administration of valacyclovir on EHV-5 viral load measured by qPCR in blood, nasal secretions (NS) and BALF in horses with EMPF. Methods: Six horses diagnosed with EMPF. Methods: A prospective clinical trial was performed. Horses received 10 days of PO administered valacyclovir (loading dose 30 mg/kg, maintenance dose 2...
Hazlett M, Stalker M, Lake M, Peregrine A.A miniature horse which died following humane seizure from an Ontario farm was emaciated with serous atrophy of fat. Autopsy revealed hepatic atrophy and moderate periportal fibrosis. Eggs and trematodes seen in the liver were identified as Dicrocoelium dendriticum. This appears to be the first reported case of infection of equids in North America with Dicrocoelium dendriticum. Infection parDicrocoelium dendriticumhépatique chez un cheval miniature. Un cheval miniature qui est mort à la suite d’une saisie humanitaire dans une ferme de l’Ontario était émacié et avait une atrophie sére...
Harman RM, He MK, Zhang S, VAN DE Walle GR.Impaired cutaneous wound healing is common in humans, and treatments are often ineffective. Based on the significant emotional and economic burden of impaired wound healing, innovative therapies are needed. The potential of mesenchymal stromal cell (MSC)-secreted factors to treat cutaneous wounds is an active area of research that is in need of refinement before effective clinical trials can be initiated. The aims of the present study were to (i) study which MSC-secreted factors stimulate dermal fibroblast (DF) migration in vitro and (ii) evaluate the potential of these factors to promote woun...
Verhoef JNC, Allen AL, Harding JCS, Al-Dissi AN.Chronic liver disease is an important cause of illness in horses, and treatment is mainly supportive. Research into new treatment modalities for humans has shown promising data regarding metallothionein (MT), which has been shown to possess regenerative, antifibrotic, and anti-inflammatory properties. This study aimed to examine the relationship between hepatic MT expression and the histopathologic markers of hepatic inflammation, fibrosis and bile duct proliferation, as well as cellular regeneration in 77 selected cases of chronic liver disease in horses. We hypothesized that higher MT expres...
Suarez-Fuentes DG, Tatarniuk DM, Caston SS, Kersh KD, Gillen AM, Hays AM.To compare outcomes after semitendinosus tenotomy performed under standing sedation versus general anesthesia. Methods: Retrospective case series. Methods: 20 horses with fibrotic myopathy of the semitendinosus muscle. Methods: Medical records (2002-2015) of horses undergoing tenotomy of the semitendinosus muscle for the treatment of fibrotic myopathy were reviewed. Signalment, history, affected muscles, restrain method, surgical procedures, and short-term outcome as well as complications were retrieved from records. Long-term outcome (gait and athletic function) was assessed at least 6 months...
Bullone M, Joubert P, Gagné A, Lavoie JP, Hélie P.The severe form of equine asthma is associated with pathological changes of the peripheral airways and pulmonary parenchyma that are only partly described. Also, the relationship between these structural alterations and the percentage of neutrophils found within the airway lumen, assessed by bronchoalveolar lavage fluid (BALF) cytology, remains ill-defined. Objective: To examine the histological lesions associated with equine asthma during disease exacerbation and remission, and their relationship with lung function and BALF neutrophilia. Methods: Observational retrospective study. Methods: Pe...
Molín J, Asín J, Vitoria A, Sanz A, Gimeno M, Romero A, Sánchez J, Pinczowski P, Vázquez FJ, Rodellar C, Luján L.A 1-month-old Purebred Spanish Horse (PSH) foal presented with progressive hepatic failure culminating in death. Hepatic lesions were consistent with congenital hepatic fibrosis (CHF). Genetic studies in the PKHD1 gene in the affected foal revealed that it was heterozygous for the 2 previously described single-nucleotide polymorphisms (SNPs) linked to CHF in Swiss Franches-Montagnes (SFM) horses. In addition, 2 novel mutations were detected, the foal being homozygous for one of them and heterozygous for the other. Genetic studies in a healthy PSH population ( n = 35) showed a 3-fold higher gen...
Sikora M, Nowak M, Racheniuk H, Wojtysiak K, Kozdrowski R.Endometritis and endometrosis have been and still are the major reasons for infertility in mares. The diagnosis of endometritis can be based on cytology and microbiology, but endometrial biopsy is still the only way to diagnose endometrosis in the mare. Our study attempted to determine if a single biopsy using his-topathology and immunohistochemistry is sufficient to ascertain reasons for infertility in Icelandic mares. The objectives of this study were to examine the relationship between deviations in endometrial biopsies in terms of prostaglandin-endoperoxide synthase-2 (PTGS-2) and fibronec...
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...
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...
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...
Buergelt CD, Hines SA, Cantor G, Stirk A, Wilson JH.Proliferative and fibrosing interstitial lung disease was diagnosed in 20 horses submitted for necropsy between 1982 and 1985. Most of the horses were foals ranging from 3 days to 6 months in age. Six adult horses were affected. The macroscopic and microscopic characteristics of the lesions consisted of proliferative interstitial pneumonia and were similar to those of atypical interstitial pneumonia of ruminants. Based on morphologic features of the lesions, a toxic etiology is suspected for the induction of this naturally acquired primary equine lung disorder, but could not be specifically di...
Williams KJ, Derksen FJ, de Feijter-Rupp H, Pannirselvam RR, Steel CM, Robinson NE.Exercise-induced pulmonary hemorrhage (EIPH) is common in horses following intense exertion, occurring in up to 75% of racing Thoroughbreds and Standardbreds. In spite of this, the pathogenesis of EIPH is poorly understood. In 7 racing Thoroughbred horses with EIPH, 6 sections were collected from the left and right lung, representing the cranial, middle, and caudal region of the dorsal and ventral lung (84 sites total). Grossly, both right and left lungs had numerous dark brown to blue-black foci along the caudodorsal visceral pleura. Tissue sections were stained with hematoxylin-eosin, Masson...
Buss DG, Sharma A, Giuliano EA, Mohan RR.Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in vitro model. Methods: An in vitro model of equine corneal fibroblast (ECF) developed was used. The ECF or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFbeta1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion...
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...
Smedley RC, Earley ET, Galloway SS, Baratt RM, Rawlinson JE.Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is a painful progressive condition of older horses that involves multiple teeth, including canines and incisors. EOTRH is uncommonly recognized by veterinary pathologists and in some cases may be misdiagnosed as cementoblastoma. The cause is unknown. The goals of this study were to describe the histopathologic features of EOTRH in 17 affected horses from the United States and to increase awareness of this condition. Samples ranged from affected tooth to the entire rostral mandible and maxilla. Affected teeth exhibited cemental h...
Desjardins I, Theoret C, Joubert P, Wagner B, Lavoie JP.Airway remodeling may play an important role in heaves pathophysiology. Transforming growth factor-beta 1 (TGF-beta1) is a potent profibrotic cytokine, which might contribute to airway wall thickening and fibrosis of bronchiolar and alveolar submucosa. An ELISA designed for the measurement of human TGF-beta1 was used to measured total TGF-beta1 released in bronchoalveolar lavage fluid (BALF) of normal horses and of those affected with heaves in remission. The specificity of the assay for TGF-beta1 of the horse was confirmed using recombinant equine TGF-beta1. The influence of hay exposure on T...
Nixon C, Chambers G, Ellsmore V, Campo MS, Burr P, Argyle DJ, Reid SW, Nasir L.Equine sarcoids are benign fibroblastic skin tumours affecting equids worldwide. Whilst the pathogenesis is not entirely understood, infection with Bovine Papillomavirus (BPV) types 1 and 2 has been implicated as a major factor in the disease process, however the mechanism by which BPV infection contributes to sarcoid pathology is not clear. In this study, we show that the majority of sarcoids express the BPV-1 major transforming gene E6. Further, we demonstrate that sarcoid lesions are not associated with high levels of cellular proliferation as assessed by Ki67 expression or with expression ...
Baker JR, Leyland A.In a histological survey of 244 tumerous growths from 155 horses, the tumours commonly found were fibromas, squamous cell carcinomas, sarcoids and papillomas, most frequently affecting the skin, external genitalia, eye and orbit. The histological features that differentiate fibroblastic citaneous growths are detailed so that the clinical behaviour of these distinct neoplasms can be studied.
Nomura M, Hosaka Y, Kasashima Y, Ueda H, Takehana K, Kuwano A, Arai K.The DNA microarray analysis for matrix metalloproteinase (MMP)-related mRNA expression in equine superficial digital flexor tendinitis indicated that mRNA level of MMP-13 was apparently up-regulated in the tendinitis as compared to normal tendon. In situ hybridization also revealed that fibroblastic cells proliferated in the granulation tissue generated in the tendinitis actively expressed MMP-13 mRNA. On the other hand, in normal tendon, a few fibroblastic cells and vascular components lied in the endotenon barely expressed its mRNA, but other cellular components in the tendon bundle were not...
Drögemüller M, Jagannathan V, Welle MM, Graubner C, Straub R, Gerber V, Burger D, Signer-Hasler H, Poncet PA, Klopfenstein S, von Niederhäusern R....Congenital hepatic fibrosis has been described as a lethal disease with monogenic autosomal recessive inheritance in the Swiss Franches-Montagnes horse breed. We performed a genome-wide association study with 5 cases and 12 controls and detected an association on chromosome 20. Subsequent homozygosity mapping defined a critical interval of 952 kb harboring 10 annotated genes and loci including the polycystic kidney and hepatic disease 1 (autosomal recessive) gene (PKHD1). PKHD1 represents an excellent functional candidate as variants in this gene were identified in human patients with autosoma...
Derksen FJ, Williams KJ, Pannirselvam RR, de Feijter-Rupp H, Steel CM, Robinson NE.Regional veno-occlusive remodelling of pulmonary veins in EIPH-affected horses, suggests that pulmonary veins may be central to pathogenesis. The current study quantified site-specific changes in vein walls, collagen and haemosiderin accumulation, and pleural vascular profiles in the lungs of horses suffering EIPH. Objective: In the caudodorsal lung regions of EIPH-affected horses, there is veno-occlusive remodelling with haemosiderosis, angiogenesis and fibrosis of the interstitium, interlobular septa and pleura. Methods: Morphometric methods were used to analyse the distribution and accumula...
Theoret CL, Barber SM, Moyana T, Townsend HG, Archer JF.The reparative ability of equine synovium was determined by gross, histological, and ultrastructural examination. The functional potential of the synovium was estimated by examination of synovial cell organelles with transmission electron microscopy. Results from rested and exercised horses were compared to determine the effect of exercise on synovial healing. The response of synovectomized joint to exercise was evaluated with a standardized lameness examination and by gross, histological, and histochemical observations of the articular cartilage. A 7-mm diameter motorized synovial resector wa...
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...
Ganjam VK, Evans TJ.Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss in mares. Equine EPF correlates inversely with conception and successful gestation. In the modified Kenney endometrial biopsy classification system, EPF categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe fibrosis (+/-inflammation), respectively. Paraffin sections of biopsy specimens were stained with H&E, and picrosirius red (specific for fibrillar collagens types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF-beta1 and 11beta-HSD2 activities were also measure...
Cogley TP, Cogley MC.The degree of penetration into the stomach and duodenum of the horse by bot fly larvae, Gasterophilus intestinalis (De Geer) and G. nasalis (Linnaeus) (Diptera : Gasterophilidae) was evaluated. Evidence of larval perforation of the stomach or duodenum was not found on gross inspection. Palpation of the intact stomach and duodenum was not effective in establishing the existence of Gasterophilus larvae within the organs. Findings suggest that larvae of both species produce an ulcer of similar depth within the gastrointestinal wall. The ulcer depth produced by larvae did not correlate with the no...
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...
Gunson DE, Sweeney CR, Soma LR.Pathologic changes are described in 11 horses that died during racing or training; 9 died of acute pulmonary hemorrhage (exercise-induced pulmonary hemorrhage), 1 died of exsanguination, and 1 died of CNS trauma. Cardiac lesions were not found in any horse. Severe engorgement of pulmonary vessels, with hemorrhage into alveoli, airways, interstitium, and subpleural tissues, was observed in all 9 horses that died of exercise-induced pulmonary hemorrhage. Infiltration of eosinophils and/or lymphocytes around vessels and airways was seen in 6 horses. Focally extensive fibrosis was observed in the ...
Szóstek AZ, Siemieniuch MJ, Lukasik K, Galvão AM, Ferreira-Dias GM, Skarzynski DJ.Accurate regulation of the reproductive cycle and successful implantation depend on proper functioning of the endometrium. The aim of this study was to determine whether mRNA transcription of specific enzymes responsible for prostaglandin (PG) synthesis (prostaglandin-endoperoxide synthase, PTGS-2; prostaglandin F(2α) synthase, PGFS; and prostaglandin E(2) synthases, PGES) and PG concentrations in endometrial extracts would change in moderate (Kenney's Category II) and severe phases of fibrosis (Kenney's Category III; endometrosis), compared with healthy endometrium (Kenney's Category I), dur...
Altamura G, Corteggio A, Nasir L, Yuan ZQ, Roperto F, Borzacchiello G.Equine sarcoids are skin tumours of fibroblastic origin affecting equids worldwide. Bovine papillomavirus type-1 (BPV-1) and, less commonly, type-2 are recognized as etiological factors of sarcoids. The transforming activity of BPV is related to the functions of its major oncoprotein E5 which binds to the platelet-derived growth factor β receptor (PDGFβR) causing its phosphorylation and activation. In this study, we demonstrate, by coimmunoprecipitation and immunoblotting, that in equine sarcoid derived cell lines PDGFβR is phosphorylated and binds downstream molecules related to Ras-mitoge...
Alpoim-Moreira J, Fernandes C, Rebordão MR, Costa AL, Bliebernicht M, Nunes T, Szóstek-Mioduchowska A, Skarzynski DJ, Ferreira-Dias G.Collagen pathological deposition in equine endometrium (endometrosis) is responsible for infertility. Kenney and Doig's endometrial biopsy histopathological classification is the gold standard method for endometrosis evaluation, whereby blood biomarkers identification would be less invasive and could provide additional information regarding endometrosis diagnosis and fertility prognosis. This study aimed to identify blood biomarkers for endometrosis diagnosis (42 mares were used in experiment 1), and fertility assessment (50 mares were used in experiment 2). Reproductive examination, endometri...
