The endothelium in horses is a thin layer of cells lining the interior surface of blood vessels, playing a significant role in vascular function and homeostasis. It is involved in the regulation of blood flow, coagulation, and immune response. The endothelium also facilitates the exchange of substances between the bloodstream and surrounding tissues. In horses, endothelial function can be affected by various factors, including inflammation, metabolic disorders, and infectious diseases. Understanding the behavior and pathology of the endothelium is essential for comprehending equine cardiovascular health and disease mechanisms. This page gathers peer-reviewed research studies and scholarly articles that explore the structure, function, and pathological changes of the endothelium in horses.
Schnelten TA, Kästner SBR, Reineking W, Hewicker-Trautwein M, Sauter P, Neudeck S.To visualize the endothelial glycocalyx in equine intestinal vessels using electron microscopy and immunohistochemistry and to evaluate the impact of induced endotoxemia on its integrity. Unassigned: 6 healthy horses free of gastrointestinal disease were anesthetized with dexmedetomidine, ketamine, and diazepam and mechanically ventilated under isoflurane anesthesia. Jejunal venous tissue samples were collected after perfusion fixation with lanthanum nitrate before and 120 minutes after endotoxemia induced by IV administration of 30 ng·kg-1 Escherichia coli lipopolysaccharide. For transmissio...
Schwarz S, Kummer S, Klang A, Walter I, Nell B, Brandt S.Squamous cell carcinoma (SCC) is the most common malignant tumor disease in horses. It predominantly affects the ocular, oronasal, and anogenital region. Equine SCC is difficult to treat, also because important aspects of SCC development and metastasis are still unclear. We previously provided evidence that equine SCC cells can adopt a stem cell-like phenotype as a hallmark of malignant progression. Here, we investigated whether equine SCCs harbor endothelial-like tumor cells that form an alternative network of pseudo-vessels better known as vasculogenic mimicry (VM). Following histopathologic...
Zamith Cunha R, Gobbo F, Morini M, Salamanca G, Zanoni A, Bernardini C, Gramenzi A, Chiocchetti R.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...
Ren W, Zhou J, Zhu J, Zhang J, Zhao X, Yao X.The ovary is among the earliest organs to undergo age-related degeneration, limiting the reproductive potential of elite horses and constraining the growth of the equine industry. Follicular development during estrus is a key determinant of fertility, yet the molecular mechanisms underlying its decline, particularly at the level of specific ovarian cell types, remain poorly understood in equids. Here, we constructed a single-cell transcriptomic atlas to investigate ovarian changes in Kazakh horses. Using single-cell RNA sequencing (scRNA-seq), we profiled 112,861 cells from follicle-containing...
Lugo T, Myers S, Nguyen TA.In vitro models have revolutionized our understanding of biological pathways and mechanisms, offering a viable alternative to direct patient testing. However, there is a significant lack of models for different animals, particularly equine models. This study presents a novel primary cell culture extracted from a 3-year-old horse diagnosed with multisystemic eosinophilic epitheliotropic disease. Tissue samples were collected from lymph nodes at various locations. Growth curves of extracted primary cells were analyzed and the optimal conditions were assessed. Biomarkers, such as CD31, ZO-1, CD79...
Neudeck S, Sauter PK, Kutter APN, Steblaj B, Söbbeler FJ, Reiners J, Freise F, Gutiérrez Bautitsta AJ, Kästner SBR.Endotoxaemia is a significant cause of morbidity and mortality in equids due to perfusion impairment and possible destruction of the glycocalyx. To evaluate our hypothesis that endotoxaemia induces changes in global cardiovascular and haematologic parameters and compromises glycocalyx integrity, evidenced by an early rise in plasma shedding products. In vivo experiments METHODS: In a prospective, randomised, controlled experimental trial, endotoxaemia was induced with E. coli B55:O5 LPS 30 ng kg over 30 min IV in six healthy adult horses ventilated with oxygen supplemented with isoflurane. St...
Lessiak U, Melchert M, Walter I, Kummer S, Nell B, Tschulenk W, Pratscher B.Angiogenesis plays a crucial role in various physiological and pathological conditions. However, research in equine angiogenesis is relative limited, necessitating the development of suitable models. To effectively analyze angiogenesis in-vitro, it is essential to target the specific cells responsible for this process, namely endothelial cells. Human umbilical vein endothelial cells (HUVECs) are one of the most used models for studying angiogenesis in humans. Serving as an equivalent to HUVECs, we present a comprehensive isolation protocol for equine umbilical vein endothelial cells (EqUVECs...
Gomez DE, Kamr A, Gilsenan WF, Burns TA, Mudge MC, Hostnik LD, Toribio RE.Endothelial glycocalyx (EG) degradation occurs in septic humans and EG products can be used as biomarkers of endothelial injury. Information about EG biomarkers and their association with disease severity is lacking in hospitalized foals. Objective: Measure serum syndecan-1 (SDC-1), heparan sulfate (HS), angiopoietin-2 (ANG-2), aldosterone (ALD), and plasma atrial natriuretic peptide (ANP) concentrations and to determine their association with disease severity and death in hospitalized foals. Methods: Ninety foals ≤3 days old. Methods: Prospective, multicenter, longitudinal study. Foals we...
Fegraeus K, Rosengren MK, Naboulsi R, Orlando L, Åbrink M, Jouni A, Velie BD, Raine A, Egner B, Mattsson CM, Lång K, Zhigulev A, Björck HM....The control of transcription is crucial for homeostasis in mammals. A previous selective sweep analysis of horse racing performance revealed a 19.6 kb candidate regulatory region 50 kb downstream of the Endothelin3 (EDN3) gene. Here, the region was narrowed to a 5.5 kb span of 14 SNVs, with elite and sub-elite haplotypes analyzed for association to racing performance, blood pressure and plasma levels of EDN3 in Coldblooded trotters and Standardbreds. Comparative analysis of human HiCap data identified the span as an enhancer cluster active in endothelial cells, interacting with genes relevant ...
Amiri Roudbar M, Rosengren MK, Mousavi SF, Fegraeus K, Naboulsi R, Meadows JRS, Lindgren G.Elite performing exercise requires an intricate modulation of the blood pressure to support the working muscles with oxygen. We have previously identified a genomic regulatory module that associates with differences in blood pressures of importance for elite performance in racehorses. This study aimed to determine the effect of the regulatory module on the protein repertoire. We sampled plasma from 12 Coldblooded trotters divided into two endothelial regulatory module haplotype groups, a sub-elite performing haplotype (SPH) and an elite performing haplotype (EPH), each at rest and exercise. Th...
Finding EJT, Faulkner A, Nash L, Wheeler-Jones CPD.Understanding the factors which control endothelial cell (EC) function and angiogenesis is crucial for developing the horse as a disease model, but equine ECs remain poorly studied. In this study, we have optimised methods for the isolation and culture of equine aortic endothelial cells (EAoECs) and characterised their angiogenic functions in vitro. Mechanical dissociation, followed by magnetic purification using an anti-VE-cadherin antibody, resulted in EC-enriched cultures suitable for further study. Fibroblast growth factor 2 (FGF2) increased the EAoEC proliferation rate and stimulated scra...
Lessiak U, Pratscher B, Tichy A, Nell B.Anti-VEGF agents were found to have clinical implications for the successful treatment of vascular-driven diseases in humans. In this study, a detailed biological characterization of bevacizumab in a variety of in vitro assays was carried out to determine the effect of bevacizumab on equine umbilical vein endothelial cells (EqUVEC). EqUVECs were harvested from umbilical cords of clinically healthy horses and exposed to different concentrations (1, 2, 4, 6, 8 mg/mL) of bevacizumab (Avastin). Assays concerning the drug's safety (cell viability and proliferation assay) and efficacy (cell tube for...
Mora-Pereira M, Boone L, Naskou M, Wooldridge A.To evaluate ex vivo angiogenesis of equine arterial rings in response to various growth media. Methods: Facial arteries were dissected from 11 horses post-euthanasia. Equine platelet lysate (ePL) was harvested from 6 horses. Methods: Arteries were exposed to endothelial growth media (EGM) + horse serum (HS) for first sprout (FS), vascular regression (VR), and (basement membrane matrix [Matrigel]) lysis (ML) evaluation. Additional rings supplemented with (1) EGM, (2) EGM + EDTA, (3) endothelial basal media (EBM), (4) EBM + HS, or (5) EBM + human VEGF were compared for vascular network area (VNA...
Finding EJT, Elliott J, Harris PA, Menzies-Gow NJ.Previously laminitic (PL) ponies are reported to have higher blood pressure than non laminitic (NL) ponies. This relative hypertension may be related to endothelial cell dysfunction, similar to humans with metabolic syndrome. To investigate the relationship between laminitis predisposition and endothelial dysfunction, the effect of nitric oxide synthase (NOS) inhibition on the change in circulating nitric oxide (NO) concentrations and systemic blood pressure (BP) was determined. An intravenous NO sensor was used to measure changes in blood NO concentration during and after intravenous infusion...
Reyner CL, Winter RL, Maneval KL, Boone LH, Wooldridge AA.To investigate the effects of recombinant equine IL-1β on function of equine endothelial colony-forming cells (ECFCs) in vitro. Methods: ECFCs derived from peripheral blood samples of 3 healthy adult geldings. Methods: Function testing was performed to assess in vitro wound healing, tubule formation, cell adhesion, and uptake of 1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate-labeled acetylated low-density lipoprotein (DiI-Ac-LDL) by cultured ECFCs. Cell proliferation was determined by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Effects o...
Le NPK, Gerdts V, Singh B.Integrin alpha-v/beta3 (αvβ3) recognizes arginine-glycine-aspartic acid (RGD) sequences and has important functions in cell adhesion, signaling, and survival. However, the expression of integrin αvβ3 in the equine lungs and jejunum is not well understood. The objective of this study was to explore the hitherto unknown expression of integrin αvβ3 in the lungs and jejuna of the horse using light and electron immunocytochemistry. Immunohistochemistry showed integrin αvβ3 on the epithelium, the immune cells in Peyer's patches, the smooth muscle, and the endothelium of equine jejuna. In equ...
Rieger J, Kaessmeyer S, Al Masri S, Hünigen H, Plendl J.The cardiovascular system is the first functional organ in the embryo, and its blood vessels form a widespread conductive network within the organism. Blood vessels develop de novo, by the differentiation of endothelial progenitor cells (vasculogenesis) or by angiogenesis, which is the formation of new blood vessels from existing ones. This review presents an overview of the current knowledge on physiological and pathological angiogenesis in the horse including studies on equine endothelial cells. Principal study fields in equine angiogenesis research were identified: equine endothelial progen...
Winter RL, Tian Y, Caldwell FJ, Seeto WJ, Koehler JW, Pascoe DA, Fan S, Gaillard P, Lipke EA, Wooldridge AA.Endothelial colony forming cells (ECFCs) may be useful therapeutically in conditions with poor blood supply, such as distal limb wounds in the horse. Encapsulation of ECFCs into injectable hydrogel microspheres may ensure cell survival and cell localization to improve neovascularization and healing. Autologous ECFCs were isolated from 6 horses, labeled with quantum nanodots (QD), and a subset were encapsulated in poly(ethylene) glycol fibrinogen microspheres (PEG-Fb MS). Full-thickness dermal wounds were created on each distal limb and injected with empty PEG-Fb MS, serum, ECFCs, or ECFCs enca...
Windberger U, Auer R, Seltenhammer M, Mach G, Skidmore JA.From a certain level of exercise-intensity onward, hematocrit increases in horses, which brings more oxygen carriers into the bloodstream. Camels, however, when used in competitive racing could be even in need of iron supplementation and blood transfusions due to a severe reduction of their available hematocrit compared to their resting hematocrit. Since the extrinsic and intrinsic mechanical properties of camel erythrocytes (RBC) are so different compared to RBCs of other mammals, the question arises whether this observation might be a response to endurance exercise aiming at keeping the RBC ...
Ledbetter EC, Irby NL.To describe the corneal in vivo confocal microscopy (IVCM) findings in horses with putative immune-mediated keratitis (IMMK). Methods: Sixty five horses with IMMK. Methods: Horses diagnosed with IMMK were examined with a modified Heidelberg Retina Tomograph II and Rostock Cornea Module. The findings from the IVCM examinations were correlated with clinical details from ophthalmic examination and diagnostic test results. Results: Eighty eyes from 65 horses were examined. Clinical IMMK lesions were categorized as epithelial (n = 17 eyes), superficial stromal (n = 38), midstromal (n = 18), a...
Poelaert KCK, Van Cleemput J, Laval K, Descamps S, Favoreel HW, Nauwynck HJ.Short-chain fatty acids (SCFA), such as sodium butyrate (SB), sodium propionate (SPr), and sodium acetate (SAc), are metabolic end-products of the fermentation of dietary fibers. They are linked with multiple beneficial effects on the general mammalian health, based on the sophisticated interplay with the host immune response. Equine herpesvirus 1 (EHV1) is a major pathogen, which primarily replicates in the respiratory epithelium, and disseminates through the body via a cell-associated viremia in leukocytes, even in the presence of neutralizing antibodies. Infected monocytic CD172a cells and ...
Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Couck L, Van den Broeck W, Azab W, Nauwynck HJ.Equine herpesvirus 1 (EHV1) replicates in the respiratory epithelium and disseminates through the body via a cell-associated viremia in leukocytes, despite the presence of neutralizing antibodies. "Hijacked" leukocytes, previously identified as monocytic cells and T lymphocytes, transmit EHV1 to endothelial cells of the endometrium or central nervous system, causing reproductive (abortigenic variants) or neurological (neurological variants) disorders. In the present study, we questioned the potential route of EHV1 infection of T lymphocytes and how EHV1 misuses T lymphocytes as a vehicle to re...
Dini P, Daels P, Loux SC, Esteller-Vico A, Carossino M, Scoggin KE, Ball BA.The human chromosome 14 microRNA cluster (C14MC) is a conserved microRNA (miRNA) cluster across eutherian mammals, reported to play an important role in placental development. However, the expression kinetics and function of this cluster in the mammalian placenta are poorly understood. Here, we evaluated the expression kinetics of the equine C24MC, ortholog to the human C14MC, in the chorioallantoic membrane during the course of gestation. Results: We demonstrated that C24MC-associated miRNAs presented a higher expression level during early stages of pregnancy, followed by a decline later in g...
Rieger J, Hopperdietzel C, Kaessmeyer S, Slosarek I, Diecke S, Richardson K, Plendl J.Human and equine patients are known to frequently develop vascular complications, particularly thrombosis both in veins and arteries as well as in the microvasculature. Objective: The aim of the present study was to investigate and compare the angiogenic response of human and equine endothelial cells to lesions in an in vitro scratch assay. Methods: Endothelial cells from human umbilical vein (HUVEC), abdominal aorta (HAAEC) and dermal microvasculature (HDMEC) as well as equine carotid artery (EACEC) and jugular vein (EVJEC) were cultured and an elongated defect was created (scratch or "wound"...
Finding EJT, Lawson C, Elliott J, Harris PA, Menzies-Gow NJ.Microvesicles are small (up to 1 μm) vesicles found in plasma and other bodily fluids. They are recognised as part of the normal system of inter-cellular communication but altered numbers are also used as biomarkers of disease. Microvesicles have not been studied in detail in the horse but may be relevant to diseases such as laminitis. Identification of equine cell specific microvesicles was performed by developing a panel of cross reactive antibodies to use in flow cytometry to detect microvesicles of platelet, leucocyte and endothelial origin in plasma from healthy ponies and those predis...
Schneberger D, Sethi RS, Singh B.Endothelium plays an important role in maintaining the vascular barrier and physiological homeostasis. Endothelium also is fundamental to the initiation and regulation of inflammation. Endothelium demonstrates phenotypic and functional heterogeneity not only among various organs but also within an organ. One of the striking examples would be the pulmonary endothelium that participates in creating blood-air barrier. Endothelium in large pulmonary blood vessels is distinct in structure and function from that lining of the pulmonary capillaries. This chapter focuses on the comparative aspects of ...
Zizzadoro C, Caruso M, Punzi S, Crescenzo G, Zongoli F, Belloli C.Hemodynamic perturbations, partly resulting from abnormal vasoconstriction of digital vessels, have been implicated in the pathogenesis of bovine and equine laminitis. This study compared the responsiveness of isolated bovine (BDA) and equine (EDA) digital arteries to pharmacological agents that stimulate receptor systems involved in the regulation of normal vessel tone. The role of the endothelium and the short- and longer-term effects of an experimentally induced endothelial damage were also evaluated. Species-related differences were found in the vessel reactivity to all of the receptor ago...
Goehring LS, Brandes K, Ashton LV, Wittenburg LA, Olea-Popelka FJ, Lunn DP, Soboll Hussey G.Equine herpesvirus-associated myeloencephalopathy is the result of endothelial cell infection of the spinal cord vasculature with equine herpesvirus-1 (EHV-1) during cell-associated viraemia. Endothelial cell infection requires contact between infected peripheral blood mononuclear and endothelial cells. Inflammation generated during viraemia likely upregulates adhesion molecule expression on both cell types increasing contact and facilitating endothelial cell infection. Objective: Evaluating the role of anti-inflammatory drugs in decreasing endothelial cell infection with EHV-1. Methods: In vi...
Murray K, Selleck P, Hooper P, Hyatt A, Gould A, Gleeson L, Westbury H, Hiley L, Selvey L, Rodwell B.A morbillivirus has been isolated and added to an increasing list of emerging viral diseases. This virus caused an outbreak of fatal respiratory disease in horses and humans. Genetic analyses show it to be only distantly related to the classic morbilliviruses rinderpest, measles, and canine distemper. When seen by electron microscopy, viruses had 10- and 18-nanometer surface projections that gave them a "double-fringed" appearance. The virus induced syncytia that developed in the endothelium of blood vessels, particularly the lungs.
Bussche L, Van de Walle GR.Mesenchymal stromal cells (MSCs) have received much attention as a potential treatment of ischemic diseases, including ischemic tissue injury and cardiac failure. The beneficial effects of MSCs are thought to be mediated by their ability to provide proangiogenic factors, creating a favorable microenvironment that results in neovascularization and tissue regeneration. To study this in more detail and to explore the potential of the horse as a valuable translational model, the objectives of the present study were to examine the presence of angiogenic stimulating factors in the conditioned medium...
Edington N, Bridges CG, Patel JR.Eight mares were infected with equid herpesvirus-1 subtype 1 isolated from a case of equine paresis. In two mares killed at 4 d.p.i. immunofluorescence showed endothelial cell infection together with thrombosis in the rete arteriosus of the nasal mucosa and also in the spinal cord of one of these mares. Circulating platelet counts in the other six mares fell as early as 2 d.p.i. and remained depressed for seven days. Circulating immune complexes started to appear at 2 d.p.i., reached maximum levels at 10 d.p.i., but were undetectable at 28 d.p.i. Three of the six remaining mares developed vary...
West JB, Mathieu-Costello O, Jones JH, Birks EK, Logemann RB, Pascoe JR, Tyler WS.Bleeding into the lungs in thoroughbreds is extremely common; there is evidence that it occurs in essentially all horses in training. However, the mechanism is unknown. We tested the hypothesis that exercise-induced pulmonary hemorrhage (EIPH) is caused by stress failure of pulmonary capillaries. Three thoroughbreds with known EIPH were galloped on a treadmill, and after the horses were killed with intravenous barbiturate the lungs were removed, inflated, and fixed for electron microscopy. Ultrastructural studies showed evidence of stress failure of pulmonary capillaries, including disruptions...
Santschi EM, Purdy AK, Valberg SJ, Vrotsos PD, Kaese H, Mickelson JR.Overo lethal white syndrome (OLWS) is an inherited syndrome of foals born to American Paint Horse parents of the overo coat-pattern lineage. Affected foals are totally or almost totally white and die within days from complications due to intestinal aganglionosis. Related conditions occur in humans and rodents in which mutations in the endothelin receptor B (EDNRB) gene are responsible. EDNRB is known to be involved in the developmental regulation of neural crest cells that become enteric ganglia and melanocytes. In this report we identify a polymorphism in the equine EDNRB gene closely associa...
Edington N, Smyth B, Griffiths L.One of three mares in the last trimester of pregnancy became paraplegic 7 days after experimental infection with EHV-1 and was killed 10 days after infection (d.p.i.). The other two mares aborted foetuses at 12 and 14 d.p.i. In the first mare, virus was detected by immunofluorescence (IIF) and immunoperoxidase (IP) staining in endothelial cells of the endometrium, placenta and umbilical vein, but not in any other foetal tissues. In the experimentally aborted foetuses, and in two other independent field cases of abortions, endothelial cell infection was also detected in the foetuses, both in ma...
Galvão AM, Ferreira-Dias G, Skarzynski DJ.In adults, physiological angiogenesis is a rare event, with few exceptions as the vasculogenesis needed for tissue growth and function in female reproductive organs. Particularly in the corpus luteum (CL), regulation of angiogenic process seems to be tightly controlled by opposite actions resultant from the balance between pro- and antiangiogenic factors. It is the extremely rapid sequence of events that determines the dramatic changes on vascular and nonvascular structures, qualifying the CL as a great model for angiogenesis studies. Using the mare CL as a model, reports on locally produced c...
Brindley MA, Maury W.Recently, it has become evident that entry of some retroviruses into host cells is dependent upon a vesicle-localized, low-pH step. The entry mechanism of equine infectious anemia virus (EIAV) has yet to be examined. Here, we demonstrate that wild-type strains of EIAV require a low-pH step for productive entry. Lysosomotropic agents that inhibit the acidification of internal vesicles inhibited productive entry of EIAV. The presence of ammonium chloride (30 mM), monensin (30 microM), or bafilomycin A (50 nM) in the medium dramatically decreased the number of EIAV antigen-positive cells. We foun...
Huang H, Lavoie-Lamoureux A, Moran K, Lavoie JP.Little is known concerning the possible contribution of T helper 2 (Th2)-type cytokines to the recruitment of neutrophils into the lung tissue. In the present study, endothelial cells from equine pulmonary arteries were cultured in the presence of recombinant equine (re) IL-4 and reIL-5, and the cytokine mRNA expression of molecules implicated in the chemotaxis and migration of neutrophils was studied using real-time RT-PCR. The functional response of reIL-4-induced endothelial cell stimulation on neutrophil migration was also studied using a chemotaxis chamber. ReIL-4 either increased the exp...
Hedges JF, Demaula CD, Moore BD, McLaughlin BE, Simon SI, MacLachlan NJ.Expression of E-selectin on activated endothelium is a critical initial step that leads to extravasation of leucocytes during inflammation, yet E-selectin is largely uncharacterized in several animal species including the horse. We have sequenced and compared E-selectin genes derived from activated cultures of purified equine (horse), cervid (black-tailed deer) and ovine (sheep) pulmonary artery endothelial cells (ECs). Phylogenetic and amino acid sequence comparisons indicate that bovine, cervid and ovine E-selectin are similar, whereas human and equine E-selectin are more closely related to ...
Williams JK, Honoré EK, Washburn SA, Clarkson TB.We attempted to determine whether continuous and cyclic medroxyprogesterone acetate modulates the effects of estrogen on dilation of atherosclerotic coronary arteries in surgically postmenopausal female monkeys. Background: Estrogen replacement in postmenopausal women preserves normal dilator responses of atherosclerotic coronary arteries. The effects of progestins on coronary artery reactivity have not been determined. Methods: Repeated quantitative coronary angiography was used to study the effects after 1 month of 1) no hormone replacement (control) or oral administration of 2) continuous c...
Smith KC, Mumford JA, Lakhani K.Four Welsh Mountain pony mares at 3 months of gestation and one mare at 5 months were inoculated intranasally with equid herpesvirus-1 (EHV-1: Ab4 isolate) at doses of 10(5) to 10(6.6) TCID50. All five mares became infected, but no cases of paresis or abortion occurred. On days 8, 9, 11, 12 (3-month-pregnant mares) and 13 (5-month-pregnant mare) after infection, a detailed examination of the pregnant uterus was made. Small numbers of vascular lesions with EHV-1 antigen expression in endothelial cells were present in the uteri of the early gestational mares; thrombi were rare and foci of thromb...
Novensa L, Selent J, Pastor M, Sandberg K, Heras M, Dantas AP.Conjugated equine estrogen therapy is the most common hormone replacement strategy used to treat postmenopausal women. However, the ability of an individual conjugated equine estrogen to modulate NO production and, therefore, to induce cardiovascular protection is largely unknown. The effects of equine and naturally occurring estrogens on NO generation were evaluated in human aortic endothelial cells by measuring in vivo NO production, as well as NO synthase (eNOS) activity and expression. The transcriptional activity on the eNOS gene was determined by the ability of estrogen receptors (alpha ...
Dini P, Daels P, Loux SC, Esteller-Vico A, Carossino M, Scoggin KE, Ball BA.The human chromosome 14 microRNA cluster (C14MC) is a conserved microRNA (miRNA) cluster across eutherian mammals, reported to play an important role in placental development. However, the expression kinetics and function of this cluster in the mammalian placenta are poorly understood. Here, we evaluated the expression kinetics of the equine C24MC, ortholog to the human C14MC, in the chorioallantoic membrane during the course of gestation. Results: We demonstrated that C24MC-associated miRNAs presented a higher expression level during early stages of pregnancy, followed by a decline later in g...
Sasaki M, Hasebe R, Makino Y, Suzuki T, Fukushi H, Okamoto M, Matsuda K, Taniyama H, Sawa H, Kimura T.The endotheliotropism of equine herpesvirus-1 (EHV-1) leads to encephalomyelitis secondary to vasculitis and thrombosis in the infected horse central nervous system (CNS). To identify the host factors involved in EHV-1 infection of CNS endothelial cells, we performed functional cloning using an equine brain microvascular endothelial cell cDNA library. Exogenous expression of equine major histocompatibility complex (MHC) class I heavy chain genes conferred susceptibility to EHV-1 infection in mouse NIH3T3 cells, which are not naturally susceptible to EHV-1 infection. Equine MHC class I molecule...
Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Couck L, Van den Broeck W, Azab W, Nauwynck HJ.Equine herpesvirus 1 (EHV1) replicates in the respiratory epithelium and disseminates through the body via a cell-associated viremia in leukocytes, despite the presence of neutralizing antibodies. "Hijacked" leukocytes, previously identified as monocytic cells and T lymphocytes, transmit EHV1 to endothelial cells of the endometrium or central nervous system, causing reproductive (abortigenic variants) or neurological (neurological variants) disorders. In the present study, we questioned the potential route of EHV1 infection of T lymphocytes and how EHV1 misuses T lymphocytes as a vehicle to re...
Morgan RA, Keen JA, Walker BR, Hadoke PW.Endocrinopathic laminitis (EL) is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing's disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing's syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6) and horses with EL (n = 6) destined for euthanasia were recruited. We studied v...
Prieto D, Simonsen U, Hernández M, García-Sacristán A.1. Penile small arteries (effective internal lumen diameter of 300 600 microm) were isolated from the horse corpus cavernosum and mounted in microvascular myographs in order to investigate the mechanisms underlying the endothelium-dependent relaxations to acetylcholine (ACh) and bradykinin (BK). 2. In arteries preconstricted with the thromboxane analogue U46619 (3-30 nM), ACh and BK elicited concentration-dependent relaxations, pD2 and maximal responses being 7.71+/-0.09 and 91+/-1 % (n=23), and 8.80+/-0.07 and 89+/-2% (n=24) for ACh and BK, respectively. These relaxations were abolished by me...
Smith DJ, Hamblin AS, Edington N.Evidence is presented to show that activation of endothelial and leucoyte adhesion molecules is a key step in transferring virus from infected leucocytes; and determines the restricted tissue tropism. A range of tissues from 2 experimentally infected mares in late pregnancy at 4 and 8 days after infection with EHV-1 were compared with those from normal pregnant and nonpregnant mares. Rabbit antisera to equine activated endothelial cell molecules were used to identify which tissues expressed these molecules in normal nongravid and gravid mares, and to investigate whether the range of tissues wa...
Allen WR, Gower S, Wilsher S.Polyclonal antisera for vascular endothelial growth factor (VEGF) and its two main receptor molecules, VEGF-I (Flt) and VEGF-II (KDR), were used in a conventional immunocytochemical staining method to localize these angiogenic ligand molecules in the endometrium and placenta of the mare during the oestrous cycle and pregnancy. The anti-VEGF and anti-Flt sera both labelled the lumenal and glandular epithelia of the endometrium throughout the oestrous cycle and both the invasive trophoblast cells of the endometrial cups and the non-invasive trophoblast of the allantochorion in pregnancy. The ant...
Venugopal CS, Eades S, Holmes EP, Beadle RE.One of the causes of equine laminitis is hyperinsulinaemia, which may be associated with endothelial dysfunction and insulin resistance of vessels. Objective: Insulin resistance can be induced in palmar digital vessels by continued exposure to insulin in vitro. The objective was to evaluate this in vitro model for future studies. Methods: Palmar digital vessel segments were collected immediately after euthanasia from horses with normal insulin/glucose blood values. Four arterial and 4 venous rings (3 mm wide) were prepared and each ring mounted in a tissue bath, containing Tyrode's solution at...
Rieger J, Kaessmeyer S, Al Masri S, Hünigen H, Plendl J.The cardiovascular system is the first functional organ in the embryo, and its blood vessels form a widespread conductive network within the organism. Blood vessels develop de novo, by the differentiation of endothelial progenitor cells (vasculogenesis) or by angiogenesis, which is the formation of new blood vessels from existing ones. This review presents an overview of the current knowledge on physiological and pathological angiogenesis in the horse including studies on equine endothelial cells. Principal study fields in equine angiogenesis research were identified: equine endothelial progen...
Poelaert KCK, Van Cleemput J, Laval K, Descamps S, Favoreel HW, Nauwynck HJ.Short-chain fatty acids (SCFA), such as sodium butyrate (SB), sodium propionate (SPr), and sodium acetate (SAc), are metabolic end-products of the fermentation of dietary fibers. They are linked with multiple beneficial effects on the general mammalian health, based on the sophisticated interplay with the host immune response. Equine herpesvirus 1 (EHV1) is a major pathogen, which primarily replicates in the respiratory epithelium, and disseminates through the body via a cell-associated viremia in leukocytes, even in the presence of neutralizing antibodies. Infected monocytic CD172a cells and ...
Gauff F, Patan-Zugaj B, Licka TF.Insulin leads to overexpression of endothelin-1 (ET-1) in the endothelium of insulin-resistant rodents. If this is also the case in equine laminar tissue, this could explain the predisposition of insulin-resistant horses to laminitis. Objective: To investigate the effect of hyperinsulinaemia on metabolism and vascular resistance of the isolated equine digit in a model of extracorporeal perfusion. Methods: Randomised, controlled study with interventional group, with blinded evaluation of histology results. Methods: After exsanguination, equine digits (n = 11) and autologous blood were collected...
Birks EK, Mathieu-Costello O, Fu Z, Tyler WS, West JB.Thoroughbred horses develop extremely high pulmonary vascular pressures during galloping, all horses in training develop exercise-induced pulmonary hemorrhage, and we have shown that this is caused by stress failure of pulmonary capillaries. It is known that the capillary transmural pressure (Ptm) necessary for stress failure is higher in dogs than in rabbits. The present study was designed to determine this value in horses. The lungs from 15 Thoroughbred horses were perfused with autologous blood at Ptm values (midlung) of 25, 50, 75, 100 and 150 mmHg, and then perfusion fixed, and samples (d...
Oaks JL, Ulibarri C, Crawford TB.Equine infectious anaemia virus (EIAV) infection of horses is characterized clinically by recurrent episodes of fever, thrombocytopenia and anaemia. In vivo, the only site of virus replication that has been previously demonstrated for EIAV is the tissue macrophage. In this study, in situ hybridization for EIAV was combined with immunohistochemistry for cell-type-specific markers to identify infected endothelial cells. EIAV-infected endothelial cells and macrophages were detected in horses infected with either virulent wild-type or with weakly virulent tissue culture-adapted strains of EIAV. Th...
Ferreira-Dias G, Costa AS, Mateus L, Korzekwa AJ, Galvão A, Redmer DA, Lukasik K, Szóstek AZ, Woclawek-Potocka I, Skarzynski DJ.Cytokines and nitric oxide (NO) are potential mediators of luteal development and maintenance, angiogenesis, and blood flow. The aim of this study was to evaluate (i) the localization and protein expression of endothelial and inducible nitric oxide synthases (eNOS and iNOS) in equine corpora lutea (CL) throughout the luteal phase and (ii) the effect of a nitric oxide donor (spermine NONOate, NONOate) on the production of progesterone (P4) and prostaglandin (PG) E(2) and factor(s) that stimulate endothelial cell proliferation using equine luteal explants. Luteal tissue was classified as corpora...
Smith D, Hamblin A, Edington N.Antisera to activated equine endothelial cells, which detected surface molecules of 116 kD, 97 kD, 42 kD and 38 kD, were made to investigate the role of endothelial adhesion molecules in equid herpes virus 1 infection. These putative adhesion molecules could be induced by 17-beta oestradiol, chorionic gonadotrophin, or IL-2, as well as by LPS and PWM. In an in vitro flow system, using equine veins or arteries, equid herpesvirus 1 in leucocytes was only transferred to infect endothelial cells if both leucocytes and endothelial cells expressed these surface molecules. Blocking of the membrane mo...
Bottoms GD, Johnson MA, Lamar CH, Fessler JF, Turek JJ.Dispersed equine vascular endothelial cells grown in tissue culture, and freshly isolated neutrophils were used to determine direct effects of endotoxin on cyclooxygenase and lipoxygenase products. Endothelial cells (10(7)/ml) or neutrophils (2 X 10(6)/ml) were incubated with (a) buffer, (b) endotoxin (10 micrograms/ml), (c) endotoxin + flunixin meglumine (10 micrograms/ml), or (d) calcium ionophore, A23187 (10 micrograms/ml). Thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), and leukotriene C4 (LTC4) were determined in the incubation fluid by radioimmunoassay. Thromboxane and prostacyclin...
Peroni JF, Moore JN, Noschka E, Grafton ME, Aceves-Avila M, Lewis SJ, Robertson TP.Equine laminitis is a crippling condition associated with a variety of systemic diseases. Although it is apparent that the prodromal stages of laminitis involve microvascular dysfunction, little is known regarding the physiology of this vasculature. The aim of the present study was to determine the relative responses of equine laminar arteries and veins to the vasoconstrictor agonists phenylephrine (1 nM-10 microM), 5-HT (1 nM-10 microM), PGF2alpha (1 nM-100 microM), and endothelin-1 (1 pM-1 microM). We have determined that laminar veins were more sensitive, with respect to the concentration o...
