Topic:Angiogenesis
Angiogenesis in horses refers to the physiological process through which new blood vessels form from pre-existing vessels, a critical component in tissue growth, repair, and regeneration. This process is key in equine health for wound healing, reproductive functions, and the response to various injuries and diseases. Angiogenesis is regulated by a balance of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), and anti-angiogenic factors, which orchestrate the formation of new vasculature. In horses, dysregulation of angiogenesis can contribute to pathological conditions, including laminitis and certain types of cancer. This page compiles peer-reviewed research studies and scholarly articles that explore the molecular pathways, regulatory mechanisms, and clinical implications of angiogenesis in equine medicine.
Equine Models of Temporomandibular Joint Osteoarthritis: A Review of Feasibility, Biomarkers, and Molecular Signaling. Osteoarthritis (OA) of the temporomandibular joint (TMJ) occurs spontaneously in humans and various animal species, including horses. In humans, obtaining tissue samples is challenging and clinical symptoms appear late in the disease progression. Therefore, genetically modified, induced, and naturally occurring animal models play a crucial role in understanding the pathogenesis and evaluating potential therapeutic interventions for TMJ OA. Among the naturally occurring models, the equine TMJ OA model is characterized by slow, age-related progression, a wide range of clinical examinations, and ...
The Emerging Role of Hypoxic Training for the Equine Athlete. This paper provides a comprehensive discussion on the physiological impacts of hypoxic training, its benefits to endurance performance, and a rationale for utilizing it to improve performance in the equine athlete. All exercise-induced training adaptations are governed by genetics. Exercise prescriptions can be tailored to elicit the desired physiological adaptations. Although the application of hypoxic stimuli on its own is not ideal to promote favorable molecular responses, exercise training under hypoxic conditions provides an optimal environment for maximizing physiological adaptations to ...
Horse serum or equine platelet lysate increases total vascular endothelial growth factor A concentrations and correlates with vascular growth in an equine facial arterial ring assay. 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...
Unique insertion/deletion polymorphisms within histidine-rich region of histidine-rich glycoprotein in Thoroughbred horses. Histidine-rich glycoprotein (HRG) is abundant plasma protein with various effects on angiogenesis, coagulation, and immune responses. Previously, we identified the base and amino acid sequences of equine HRG (eHRG) and revealed that eHRG regulates neutrophil functions. In this study, we first conducted a large-scale gene analysis with DNA samples extracted from 1700 Thoroughbred horses and identified unique insertion/deletion polymorphisms in the histidine-rich region (HRR) of eHRG. Here we report two types of polymorphisms (deletion type 1 [D1] and deletion type 2 [D2]) containing either a 45...
Study on NGF and VEGF during the Equine Perinatal Period-Part 1: Healthy Foals Born from Normal Pregnancy and Parturition. The importance of trophic factors, such as nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) during the perinatal period, is now emerging. Through their functional activities of neurogenesis and angiogenesis, they play a key role in the final maturation of the nervous and vascular systems. The present study aims to: (i) evaluate the NGF and VEGF levels obtained at parturition from the mare, foal and umbilical cord vein plasma, as well as in amniotic fluid; (ii) evaluate NGF and VEGF content in the plasma of healthy foals during t...
Functional properties of equine adipose-derived mesenchymal stromal cells cultured with equine platelet lysate. Successful translation of multipotent mesenchymal stromal cell (MSC)-based therapies into clinical reality relies on adequate cell production procedures. These should be available not only for human MSC, but also for MSC from animal species relevant to preclinical research and veterinary medicine. The cell culture medium supplementation is one of the critical aspects in MSC production. Therefore, we previously established a scalable protocol for the production of buffy-coat based equine platelet lysate (ePL). This ePL proved to be a suitable alternative to fetal bovine serum (FBS) for equine a...
Transcriptomic and histochemical analysis reveal the complex regulatory networks in equine chorioallantois during spontaneous term labor†. The equine chorioallantois (CA) undergoes complex physical and biochemical changes during labor. However, the molecular mechanisms controlling these changes are still unclear. Therefore, the current study aimed to characterize the transcriptome of equine CA during spontaneous labor and compare it with that of normal preterm CA. Placental samples were collected postpartum from mares with normal term labor (TL group, n = 4) and from preterm not in labor mares (330 days GA; PTNL group, n = 4). Our study identified 4137 differentially expressed genes (1820 upregulated and 2317 downregulat...
Efficacy of chitosan in the treatment of chronic skin lesions in a horse: A case report. Consultation was requested for a 7-year-old Gypsy Vanner male horse with a 2-year history of foreskin injury. Upon revision, an ulcer, 153 cm2 in size, with yellowish granules was observed; a RESVECH 2.0 evaluation revealed a score of 32/35 points. Medical history confirmed multiple failed deworming, anti-inflammatory, and antibiotic treatments with different topical therapies and recurrence in summer. Laboratory results confirmed elevated total proteins (8.8 g/dL) and globulins (5.5 g/dL), negative bacterial and fungal cultures, as well as negative coproparasitoscopic findings, and finally, i...
Repair of experimentally induced femoral chondral defect in a rabbit model using Lyophilized growth promoting factor extracted from horse blood platelets (L-GFequina). Lyophilized equine platelet derived growth factors (LGF) is a novel advanced platelet rich protein growth factor. It has been successfully applied in various fields of regenerative medicine to treat a variety of inflammatory and degenerative musculoskeletal conditions. Our study aimed to evaluate the efficacy of intraarticularly injected LGF for the remedy of articular cartilage injury, commonly characterized by progressive pain and loss of joint function in osteoarthritic rabbits. Full-thickness cylindrical cartilage defects were generated in both femoral condylar articular surfaces in twenty...
The granulation (t)issue: A narrative and scoping review of basic and clinical research of the equine distal limb exuberant wound healing disorder. Exuberant granulation tissue (EGT) is often observed during second intention wound healing in horses. Despite its impact on wound care, the basic mechanisms leading to EGT are still unclear and effective strategies to prevent and/or treat EGT are lacking. The development of EGT is a poorly understood, multifactorial process involving hyperproliferating fibroblasts and malfunctional differentiation of keratinocytes, suboptimal wound contraction, dysfunctional vascularisation, and chronic inflammation. To consolidate and describe basic and clinical research literature on EGT and to identify know...
Identification of genes associated with susceptibility to persistent breeding-induced endometritis by RNA-sequencing of uterine cytobrush samples. This study aimed to investigate the susceptibility to persistent breeding-induced endometritis (PBIE). Cytobrush samples were collected from 81 broodmares 1-3 days before artificial insemination (AI). Susceptibility to PBIE was evaluated by the presence of ≥ 2 cm of intrauterine fluid 24 h after AI, besides the fertility was determined by a sonographic pregnancy diagnosis 2 weeks after ovulation. RNA expressions were compared between susceptible non-pregnant (SNP) mares (n=9) and resistant pregnant (RP) mares (n=9) as well as between susceptible pregnant (SP) mares (n=9) and susceptible non-...
Growth Factor Roles in Soft Tissue Physiology and Pathophysiology. Repair and healing of injured and diseased tendons has been traditionally fraught with apprehension and difficulties, and often led to rather unsatisfactory results. The burgeoning research field of growth factors has opened new venues for treatment of tendon disorders and injuries, and possibly for treatment of disorders of the aorta and major arteries as well. Several chapters in this volume elucidate the role of transforming growth factor β (TGFß) in pathogenesis of several heritable disorders affecting soft tissues, such as aorta, cardiac valves, and tendons and ligaments. Several member...
Estrogens Regulate Placental Angiogenesis in Horses. A sufficient vascular network within the feto-maternal interface is necessary for placental function. Several pregnancy abnormalities have been associated with abnormal vascular formations in the placenta. We hypothesized that growth and expansion of the placental vascular network in the equine () placenta is regulated by estrogens (estrogen family hormones), a hormone with a high circulating concentration during equine gestation. Administration of letrozole, a potent and specific inhibitor of aromatase, during the first trimester (D30 to D118), decreased circulatory estrone sulfate concentrat...
Equine ovarian tissue xenografting: impacts of cooling, vitrification, and VEGF. Ovarian tissue transplantation methods using cooled and cryopreserved samples have been attractive options for fertility preservation in animal models and humans. The aim of this study was to evaluate the impact of previous exposure to cooling, cryopreservation, and VEGF on the overall efficiency of equine ovarian tissue after heterotopic xenotransplantation in mice. The end points evaluated were follicular morphology and development, follicular and stromal cell densities, angiogenesis (i.e. the density of new and mature blood vessels), collagen types I and III fiber densities, and total fibro...
Endometrial angiogenesis induced by uterine insufflation with an oxygen-ozone gas mixture in mares. Ozone (O ) therapy has been used to improve peripheral tissue oxygenation in humans and domestic animals. The goal of the present study was to characterize histological changes in the endometria of healthy equines following tissue exposure to gas mixtures enriched with different concentrations of O . Cycling mares without endometrial degeneration were divided into three groups according to treatment (n = 9 mares/group). The uteri from the O , ½O and control groups were insufflated for 3 min with gas containing 42, 21 and 0 μg O ml , respectively. Treatments were performed every three da...
Bronchial angiogenesis in horses with severe asthma and its response to corticosteroids. Severe asthma in horses is characterized by structural changes that thicken the lower airway wall, a change that is only partially reversible by current treatments. Increased vascularization contributes to the thickening of the bronchial wall in humans with asthma and is considered a potential new therapeutic target. Objective: To determine the presence of angiogenesis in the bronchi of severely asthmatic horses, and if present, to evaluate its reversibility by treatment with corticosteroids. Methods: Study 1: Bronchial samples from asthmatic horses in exacerbation (7), in remission (7), and a...
Equine cervical remodeling during placentitis and the prepartum period: a transcriptomic approach. Cervical remodeling is a critical component in both term and preterm labor in eutherian mammals. However, the molecular mechanisms underlying cervical remodeling remain poorly understood in the mare. The current study compared the transcriptome of the equine cervix (cervical mucosa (CM) and stroma (CS)) during placentitis (placentitis group, n = 5) and normal prepartum mares (prepartum group, n = 3) to normal pregnant mares (control group, n = 4). Transcriptome analysis identified differentially expressed genes (DEGs) during placentitis (5310 in CM and 907 in CS) and during the normal prepartu...
Correlations of corpus luteum blood flow with fertility and progesterone in embryo recipient mares. The aim of this study was to evaluate the correlation between the corpus luteum vascularization with the concentration of progesterone and the fertility of embryo recipient mares. Mangalarga Marchador mares (n = 33) were distributed into groups according to the days (D) after ovulation, as follows: D3 (n = 8), D4 (n = 8), D5 (n = 9), and D6 (n = 8). The evaluations of the corpus luteum, endometrium, and blood collection to quantify the progesterone concentration were carried out on D3, D4, D5, and D6. Among the parameters evaluated, only progesterone concentration on D6 differed from the other...
Histidine-Rich Glycoprotein Functions as a Dual Regulator of Neutrophil Activity in Horses. Histidine-rich glycoprotein (HRG) is an abundant plasma protein that has been identified in most mammals. We first identified whole genome sequence of equine HRG (eHRG) and succeeded to purify eHRG from plasma of horses. Since HRG interacts with various ligands, this protein is thought to be involved in immune response, coagulation, and angiogenesis. Systemic inflammatory response syndrome (SIRS) is characterized as a non-specific, clinical, pro-inflammatory immune response that damage organs and tissues in the host. Recent reports revealed that blood HRG levels in human patients with SIRS are...
Microvascularization and Expression of Fibroblast Growth Factor and Vascular Endothelial Growth Factor and Their Receptors in the Mare Oviduct. The oviduct presents the ideal conditions for fertilization and early embryonic development. In this study, (i) vascularization pattern; (ii) microvascular density; (iii) transcripts of angiogenic factors (, , ) and their receptors-, , , respectively, and (iv) the relative protein abundance of those receptors were assessed in cyclic mares' oviducts. The oviductal artery, arterioles and their ramifications, viewed by means of vascular injection-corrosion, differed in the infundibulum, ampulla and isthmus. The isthmus, immunostained with CD31, presented the largest vascular area and the highest ...
Effect of recombinant equine interleukin-1β on function of equine endothelial colony-forming cells in vitro. 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...
Paternally expressed retrotransposon Gag-like 1 gene, RTL1, is one of the crucial elements for placental angiogenesis in horses†. RTL1 (retrotransposon Gag-like 1) is an essential gene in the development of the human and murine placenta. Several fetal and placental abnormalities such as intrauterine growth restriction (IUGR) and hydrops conditions have been associated with altered expression of this gene. However, the function of RTL1 has not been identified. RTL1 is located on a highly conserved region in eutherian mammals. Therefore, the genetic and molecular analysis in horses could hold important implications for other species, including humans. Here, we demonstrated that RTL1 is paternally expressed and is localized...
Mesenchymal stem cell transplantation into the spinal cord of healthy adult horses undergoing cervical ventral interbody fusion. To determine the feasibility of umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation into the cervical spinal cord of horses by using fluoroscopy with or without endoscopic guidance and to evaluate the neurological signs and tissue reaction after injection. Methods: Experimental study. Methods: Eight healthy adult horses with no clinical signs of neurological disease. Methods: After cervical ventral interbody fusion (CVIF), ten million fluorescently labeled allogeneic UC-MSC were injected into the spinal cord under endoscopic and fluoroscopic guidance (n = 5) or fluoroscopic...
Isolation of Mammalian Mesoangioblasts: A Subset of Pericytes with Myogenic Potential. Mesoangioblasts (MABs) are vessel-associated stem cells that express pericyte markers and are originally isolated from the embryonic dorsal aorta. From postnatal small vessels of skeletal muscle and heart, it is possible to isolate cells with similar characteristics to embryonic MABs. Adult MABs have the capacity to self-renew and to differentiate into cell types of mesodermal lineages upon proper culture conditions. To date, the origin of MABs and the relationship with other muscle stem cells are still debated. Recently, in a phase I-II clinical trial, intra-arterial HLA-matched MABs were pro...
Transcriptomic analysis of equine placenta reveals key regulators and pathways involved in ascending placentitis†. Improved understanding of the molecular mechanisms underlying ascending equine placentitis holds the potential for the development of new diagnostic tools and therapies to forestall placentitis-induced preterm labor. The current study characterized the equine placental transcriptome (chorioallantois [CA] and endometrium [EN]) during placentitis (placentitis group, n = 6) in comparison to gestationally-matched controls (control group, n = 6). Transcriptome analysis identified 2953 and 805 differentially expressed genes in CA and EN during placentitis, respectively. Upstream regulator analys...
Differential gene expression analysis reveals pathways important in early post-traumatic osteoarthritis in an equine model. Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression c...
Equine small intestinal angiomatosis. Multiple red, raised nodules multifocally distributed along the serosal surface of the normal and the nonviable jejunum were identified in a 24-year-old neutered male horse undergoing surgery for removal of the strangulating lipoma around the jejunum. Histologically, these nodules consisted of many significantly and variably dilated, blood-filled vascular channels lined by a single layer of flattened, well-differentiated endothelial cells with occasional thrombi within a mildly thickened fibrous stroma. A diagnosis of intestinal angiomatosis was proposed. To the best of the authors' knowledge,...
Heterotopic autotransplantation of ovarian tissue in a large animal model: Effects of cooling and VEGF. Heterotopic and orthotopic ovarian tissue autotransplantation techniques, currently used in humans, will become promising alternative methods for fertility preservation in domestic and wild animals. Thus, this study describes for the first time the efficiency of a heterotopic ovarian tissue autotransplantation technique in a large livestock species (i.e., horses) after ovarian fragments were exposed or not to a cooling process (4°C/24 h) and/or VEGF before grafting. Ovarian fragments were collected in vivo via an ultrasound-guided biopsy pick-up method and surgically autografted in a subcutan...
Bisphosphonates in veterinary medicine: The new horizon for use. Bisphosphonates (BPs) are characterized by their ability to bind strongly to bone mineral and inhibit bone resorption. However, BPs exert a wide range of pharmacological activities beyond the inhibition of bone resorption, including the inhibition of cancer cell metastases and angiogenesis and the inhibition of proliferation and apoptosis in vitro. Additionally, the inhibition of matrix metalloproteinase activity, altered cytokine and growth factor expression, as well as reductions in parameters of pain have also been reported. In humans, clinical BP use has transformed the treatment of post-m...
Washed Equine Platelet Extract as an Anti-Inflammatory Biologic Pharmaceutical. Mammalian platelets participate in the immediate tissue injury response by initiating coagulation and further promoting tissue injury mitigation and repair. The latter properties are deployed following platelet release of presynthetized morphogens, cytokines, and growth and chemotactic factors, which launch a tissue regenerative, angiogenic, and anti-inflammatory program. Several blood-derived biologic products, like platelet-rich plasma (PRP) and platelet lysate (PL), are currently on the market to allow proper healing and tissue regeneration. However, not all growth factors are released from...