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Topic:Fibrosis
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.
Morphological investigation of myocardial sleeves with potential relevance to atrial fibrillation in Norwegian-Swedish Coldblooded Trotters. Myocardial sleeves (MSs) are thin layers of cardiac muscle that extend from the atria into the caval and pulmonary veins. They are recognised as important structures in both initiating and maintaining atrial tachycardia, and especially atrial fibrillation (AF), which is the most clinically important cardiac arrhythmia in horses with a reported prevalence of 1.3-2% in Standardbred racehorses. In contrast, the Norwegian-Swedish Coldblooded Trotter (NSCT) has a much lower prevalence of AF despite experiencing similar physical demands. The purpose of this study was to describe the macro-, and micr...
Interleukin 12 on extracellular matrix-related factors and functional characteristics of equine endometrial fibroblasts. Tissue fibrosis is described as the excessive accumulation of extracellular matrix (ECM) components. This process is associated with inflammation, and the interaction between fibroblasts and immune cells plays a key role, driving the progression of fibrosis. Results of recent study suggest that interleukin (IL)-12 may play a role in the processes associated with the development of fibrosis. This proinflammatory cytokine is synthesized and released by macrophages, dendritic cells, and B cells. Objective: The objective of this study was to determine: (i) the expression of IL-12 and its receptor ...
Exploring the role of epigenetics in the processes related to the development of endometrosis in the mare. Endometrosis is a chronic degenerative condition of the mare endometrium characterized by progressive fibrosis and glandular alterations that impair uterine function and fertility. Its pathogenesis involves persistent inflammation, the activation of myofibroblasts, and the accumulation of extracellular matrix (ECM), leading to disrupted glandular secretion and compromised maintenance of pregnancy. While histopathological studies of endometrosis are well described, the underlying molecular mechanisms remain incompletely understood. Emerging evidence highlights the crucial role of epigenetic reg...
Signal-averaged electrocardiography in horses: characteristics of ventricular late potentials in healthy Thoroughbreds and horses with cardiac abnormalities. Sudden death in horses, often attributed to lethal arrhythmias, poses significant welfare and economic risks, yet its prediction remains challenging. This study aimed to characterize ventricular micro-potentials using signal-averaged electrocardiography (SAECG) and evaluate their potential for assessing sudden death risk. High-resolution orthogonal X-, Y-, and Z-lead ECGs were recorded in 24 healthy Thoroughbreds (aged 2-31 years), one horse with bupivacaine-induced myocardial injury, and three horses with persistent pathological murmurs. SAECG parameters, including filtered QRS duration (fQRS...
Miscellaneous Equine Liver Conditions. Miscellaneous equine liver conditions not covered in other chapters include chronic active hepatitis, Tyzzer's disease, seasonal idiopathic hepatitis, neoplasia, and idiopathic persistent hyperbilirubinemia. Chronic active hepatitis refers to inflammatory and fibrotic liver disease with an unknown cause. Treatment is aimed at reducing inflammation. Tyzzer's disease is caused by Clostridium piliforme infection and causes acute necrotizing hepatitis in foals. Successful treatment with antimicrobial therapy and supportive care is rare. Seasonal idiopathic hepatitis is a winter disease of Midweste...
Prognosis of Equine Liver Diseases. Prognostic information in equine liver disease can be gleaned from historical, clinical, clinicopathological, ultrasonographic, and histopathological features. However, given the multiple causes and subtypes of liver disease affecting horses worldwide, prognostic data might not be suitable for universal application across all cases. Most evidence has been established for horses with chronic hepatopathies and extrapolation to acute cases should be avoided. In chronic liver disease the presence and severity of clinical signs and serum markers including total globulins, albumin, and bile acids ar...
Activity of 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester lipase in peritoneal fluid may be associated with strangulating lesions, pancreatic fibrosis, and negative outcome in horses with colic. To compare plasma and peritoneal 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase activity between horses with and without colic signs and document pancreatic histopathology in a subset of horses. Unassigned: This prospective, cross-sectional study included university-owned or donated healthy horses and client-owned horses presenting to the veterinary teaching hospital for colic. Peritoneal WBC and lactate concentrations and plasma and peritoneal DGGR lipase activity were measured. Pancreatic tissue was collected via convenience sampling. Pancreatic fibrosis ...
Multiple strategies, one mission: mesenchymal stromal cell-based mechanisms of action in osteoarthritis. Osteoarthritis (OA) is a cross-species, multifactorial joint disease characterized by the progressive degeneration of articular cartilage, morphological remodeling of the subchondral bone, and inflammatory and fibrotic changes of the joint capsule. These alterations arise from chronic, often subclinical, inflammatory processes and dysregulated cellular homeostasis, leading to profound shifts in the cellular and extracellular composition of the joint organ. Although the mechanisms driving persistent inflammation are only partially understood, their impact on all joint-associated tissues is well...
Milk fat globule EGF and factor V/VIII domain containing (MFGE8) as a novel player in equine endometrial fibrosis. With increasing age, mares are frequently affected by endometrial fibrosis. Transforming growth factor beta 1 (TGF-β1) promotes fibrosis, while milk fat globule EGF and factor V/VIII domain containing (MFGE8) primarily exerts antifibrotic effects. We used in situ hybridization analysis (ISH) to investigate MFGE8, TGFB1 and its downstream effectors cellular communication network factor 2 (CCN2) and transgelin (TAGLN) in equine endometrial fibrosis. Additionally, transcriptional effects of TGF-β1 and MFGE8 on equine endometrial fibroblasts in vitro were investigated by single cell sequencing. ...
Pulmonary fibrosis in horses associated with spontaneous Crotalaria juncea intoxication. We report an outbreak of Crotalaria juncea intoxication in horses exhibiting progressive weight loss and respiratory distress in northeastern Brazil. Necropsy revealed firm, non-collapsed lungs with extensive interstitial fibrosis, bronchiolar epithelial hyperplasia with club cells proliferation, and marked pulmonary arterial remodeling. Hepatic lesions consisted primarily of centrilobular necrosis, probably resulting from hypoxic injury related to anemia and prolonged agonic death. Pasture inspection identified significant invasion by shrubs of C. juncea in various phenological stages.
Interleukin-4 changes the transcriptome, ECM-associated components and function of mare endometrial fibroblast: Insights from healthy and fibrotic cells. Fibrosis remains incompletely understood, particularly in terms of how immune mediators shape stromal programs. We used a spontaneous large‑animal model-endometrosis (equine endometrial fibrosis) to define how interleukin‑4 (IL‑4) reprograms fibroblasts from healthy and fibrotic endometrium. Primary fibroblasts were exposed to IL‑4 (10 ng/mL) for 48 or 96 h. At 48 h, bulk transcriptomes revealed 1307 differentially expressed genes (DEGs; 648 up, 659 down) and 1271 DEGs (645 up, 626 down) in fibroblasts derived from endometria without or with endometrosis, respectively. Enrichment an...
TGF-β1 and estradiol modulate prostaglandin concentrations and related gene expression in equine endometrium during the follicular phase. Transforming growth factor (TGF)-β1 is a pro-fibrotic cytokine that affects extracellular matrix (ECM) deposition and fibroblast activity. 17β-Estradiol (E), the dominant ovarian steroid during the follicular phase (FLP) of the estrous cycle, can also influence ECM remodeling and fibrosis, through prostaglandin (PG) synthesis. PGs have opposing roles in fibrosis, with PGE₂ showing anti-fibrotic effects and PGF₂α promoting fibrosis. Equine endometrosis, whose main pathological feature is fibrosis, is marked by chronic inflammation and ECM accumulation, and may involve mediators like TGF-...
Amniotic Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles for Equine Chronic Degenerative Endometritis Treatment. Equine chronic degenerative endometritis (CDE) is a progressive process characterized by endometrial fibrosis that could be responsible for alterations of uterine environment and foetal-maternal communication. Objective: The aim of this study was to try to restore this communication by intrauterine administrations of amniotic cell-derived extracellular vesicles (AMC-EVs) in a case series. Methods: Twelve mares were selected on the basis of their reproductive history of early embryonic loss or abortion and clinical suspicion of CDE subsequently verified with histopathological examination of end...
Full Clinical Pathological and Bacteriological Investigation of a Giant Nasal Polyp Associated With the Developing Apex of the Permanent Fourth Premolar (Triadan 108) in a 3-year-old Connemara Filly: A Case Report. A 3-year-old Connemara X filly was referred to a UK equine hospital for further investigation of unilateral nasal discharge and facial swelling. Diagnostic imaging documented the presence of a heterogenous, soft tissue opacity with areas of focal mineralisation within the right paranasal sinuses, completely obliterating the nasal cavity, in addition to endodontic disease and significant periapical pathology associated with the right permanent fourth premolar (Triadan 108). Subsequent histopathologic examination confirmed the mass as a fibro-inflammatory polyp.
Cannabinoid and cannabinoid related receptors in fibroblasts, inflammatory and endothelial cells of the equine hoof with and without laminitis: novel pharmacological target. Evidence suggests that the endocannabinoid system (ECS) is crucial for regulating inflammation, cell proliferation and pain. The ECS is composed of cannabinoid receptors such as type 1 (CBR1), type 2 (CBR2) and GPR55, endocannabinoids and enzymes. Proteins of ECS have previously been localized in the epidermal cells of the horse hooves. Given the physio-pathological role and cellular distribution of the ECS across species, the authors hypothesized that cannabinoid receptors are expressed within the inflammatory cells, fibroblasts and endothelial cells of the equine hoof laminae, going beyond t...
Towards understanding mare endometrosis: ex vivo study on the role of relaxin. Mare endometrosis remains a poorly understood pathological process. Objective: Mare endometrial tissue with endometrosis was used to determine the effects of relaxin (RLX). Healthy tissues that were left untreated (H), or treated with vehicle (Hveh), and tissues with endometrosis that were left untreated (E), treated with vehicle (Eveh), and treated with RLX (10, 25, 50 nM; ER) were used for an ex vivo system for 72 h. Methods: Tissue histological examination, and immunoenzymatic measurement of the concentrations of transforming growth factor β (TGF-β), interleukins (IL-6 and IL-8), and pr...
Uterine proteomic and cytokine profiling show that Streptococcus equi subsp. zooepidemicus induces immune-metabolic dysregulation and may predispose mares to endometrosis. This study aims to characterize and compare the uterine fluid proteome and cytokine profile of reproductively healthy mares (HM; n = 15) and mares with Streptococcus equi subsp. zooepidemicus (S. zooepidemicus)-associated endometritis (SAE; n = 9). Uterine flush samples collected during the follicular phase were analyzed by shotgun proteomics and multiplex cytokine assays. Equine proteins were mapped to human orthologs, and enrichment and network analyses were performed using g:Profiler, Metascape, ToppGene, and STRING/MCODE. SAE mares showed higher levels of IL-1α, IL-1β, GRO, IL12p...
Transcriptomic Insights into Tumor Necrosis Factor α’s Role in the Fibrosis-Related Processes of Equine Endometrial Fibroblasts. Equine endometrosis is a chronic degenerative condition of the endometrium. A hallmark feature of endometrosis is endometrial fibrosis accompanied by degenerative changes in the adjacent tissue structure. Tumor necrosis factor α (TNFα), a pleiotropic cytokine produced by various immune cells, plays a dual role in coordinating immune responses and regulating cell/tissue homeostasis, making it an important regulator of fibrotic-related disorders. However, the exact role of TNFα in the development of equine endometrial fibrosis remains to be discovered and explained. Therefore, the main aim of...
Collagen composition in equine exuberant granulation tissue reflects tissue immaturity. Exuberant granulation tissue (EGT) is a second intention wound healing disorder. It commonly occurs in the distal limb of horses. EGT causes significant increase in the duration and cost of treatment, potentially leading to the decision not to pursue treatment and euthanize the patient. The underlying pathomechanisms of this fibroproliferative disorder remain unclear, particularly in terms of collagen composition and the association between myofibroblasts and blood vessels. This study investigated the collagen composition in naturally occurring EGT following trimming in 19 horses (EGT group). ...
Retrospective Analysis of Suspensory Ligament Branch Injuries in 70 Dressage Horses. There are no studies that have investigated factors influencing the outcome of dressage horses with suspensory ligament (SL) branch injuries. The aim was to determine if age, breed, work level, injury severity, anatomical localisation of injury, number of injured branches, periligamentous fibrosis, persistence of power Doppler signal or coexistent osteoarthritis of a metacarpophalangeal (MCP) or metatarsophalangeal (MTP) joint influenced the prognosis of 70 dressage horses. Outcome was defined as good (return to pre-injury level of work or higher), poor (return to a lower level of work) or ret...
Th1 and Th2 cells in equine endometrosis and their interactions with endometrial fibroblasts. Mare endometrosis is a chronic degenerative condition of the endometrium, primarily characterized by fibrosis, involving interactions among fibroblasts, immune cells, and epithelial cells regulated by cytokines and growth factors. T helper (Th)1 and Th2 cells seem to play a pivotal role in fibrosis. However, their roles in equine endometrial fibrosis remain unknown. This study explores Th1 and Th2 cell distribution across different stages of endometrium histopathological Kenney and Doig categories; and evaluated their secretome effects on non-fibrotic endometrium derived fibroblast functional ...
Proteomic profiling of endometrial tissue and plasma from mares with endometrial fibrosis†. Endometrial fibrosis leads to subfertility when periglandular fibrosis impairs endometrial gland function. Identifying distinct protein expressions in mares suffering from this condition is essential for understanding the pathogenesis and developing treatments to delay fibrotic progression. To gain a better understanding of protein dynamics underlying this condition, Data-Independent Acquisition Mass Spectrometry was utilized to comprehensively characterize and compare the equine endometrial and plasma proteome from mares with different severities of endometrial fibrosis. Mares in diestrus wer...
Interleukin 17A in the fibrotic-related processes in endometrosis in the mare. Equine endometrosis is a chronic degenerative condition with fibrosis being one of the most significant characteristics. A growing body of evidence indicates the critical role of interleukin (IL)-17 in fibrotic disorders. However, its exact role during equine endometrosis remains to be discovered and explained. The main aim of the current study was to establish the expression of IL-17A signaling components in equine endometria with and without endometrosis as well as the effects of IL-17A on the transcriptomic signature, cellular functional characteristics, expression of extracellular matrix (...
Extracellular Vesicles Derived From Endometrial Stem Cells Preconditioned With PGE2-Reverse Myofibroblast Phenotype in Mare Endometrial Cells: A Novel Anti-Fibrotic Approach. Endometrial fibrosis in mares compromises fertility through aberrant extracellular matrix deposition and sustained myofibroblast activation. Conventional interventions fail to reverse these pathological alterations, necessitating innovative, mechanism-focused therapies. In this study, we pioneered the use of prostaglandin E2 (PGE2) preconditioning of equine endometrial-derived mesenchymal stem cells (ET-eMSCs) and their extracellular vesicles (EVs) to target fibrotic processes directly. ET-eMSCs were isolated from mare endometrial biopsies pretreated with PGE2 to enhance their anti-fibrotic se...
Morphological and morphometric characterization of the aorta of Brazilian horses (Equus ferus caballus, Linnaeus-1758): Comparative analysis of the aortic bulb and ascending aorta. We examined 52 horse aortas to characterize the morphological aspects of the aortic bulb wall and the ascending aorta. The morphometric data were analyzed using ImageJ®-Fiji 1.5 software. The Tunica intima was composed of endotheliocytes with scarce cytoplasm and ellipsoid nuclei, supported by a collagenous subendothelial stratum. The Tunica media was composed entirely of fascicles of vascular smooth muscle cells interspersed with bundles of collagen fibers and elastic lamellae, characterizing the aortic medial lamellar unit. The Tunica adventitia consisted of two distinct sub-layers: the ext...
The equine placental extract ameliorates renal damage in mice with adenine-induced chronic kidney disease by inhibiting indoxyl sulfate production. Indoxyl sulfate (IS) is a dietary metabolite of tryptophan that is produced in the liver. It is a uremic toxin that facilitates the progression of chronic kidney disease (CKD). We previously observed that equine placental extract (ePE) inhibited IS synthesis in an inhibition assay using the liver S9 fraction. Unassigned: This study was designed to investigate the effects of ePE on adenine-induced renal failure in mice at the histological and molecular levels to understand the mechanism of action of ePE. Unassigned: We assessed this effect through biochemical and histological analyses using a...
Substrate stiffness modifies gene expression and transcriptional response of equine endometrial fibroblasts to TGF-β1. Equine endometrial fibrosis is a leading cause of subfertility in aging mares. Fibrosis is a reparative response involving excess deposition of extracellular matrix (ECM) and increasing tissue stiffness. Augmented rigidity itself can drive fibrosis, by stimulating transition from fibroblasts to myofibroblasts. Myofibroblasts release latent transforming growth factor beta 1 (TGF-β1) from the ECM, thereby activating this profibrotic cytokine. Tissue culture polystyrene (TCP) is commonly used for in vitro experiments. The endometrium, however, is considerably softer than TCP. This study critical...
Integrated proteomics highlights functional activation induced by advanced-platelet rich fibrin plus (A-PRF +) in primary equine fibroblasts. Wounds are common in equine practice, and often lead to complications such as infections, delayed healing and hypertrophic scarring, which can be costly and difficult to manage. Developing affordable and effective treatments has become an increasingly important focus in veterinary research. Equine advanced-platelet-rich fibrin plus (A-PRF+) demonstrates regenerative properties comparable to its human counterpart, but cellular-level investigations exploring its molecular mechanisms remain limited. This study aimed to investigate the in vitro effects of equine A-PRF + on primary fibroblast ...
Histological and morphometric changes in cardiac conduction fibers after spontaneous myocardial infarction in horses and dogs. Arrhythmic sudden cardiac death in dogs and horses often results from ventricular arrhythmia secondary to myocardial damage. Despite this, limited data exist on the histomorphometric changes in cardiac conduction fibers (CCFs) and cardiac conduction cells (CCCs) following spontaneous myocardial infarction (MI). This study aimed to characterize morphometric and histological alterations in conduction fibers and their junctions with cardiomyocytes in infarcted hearts of horses and dogs. Unassigned: Ten hearts from horses and 10 from dogs that had died suddenly were examined. Histological and immu...
The effect of amphiregulin on equine endometrial fibroblasts: in vitro responses of fibroblast derived from non-fibrotic and fibrotic endometrium. The role of AREG in the development of fibrosis in the progression of endometrosis in mare remains unknown. We aimed to determine the effects of AREG on fibroblast functional characteristics as well as the expression of extracellular matrix (ECM)-associated genes in fibroblast derived from non-fibrotic and fibrotic equine endometria. Our findings suggest that the mechanisms associated with ECM remodeling regulated by AREG in non-fibrotic fibroblasts may be dysregulated in the progression of fibrosis in endometrosis.
