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.
Angiographic anatomy of the extracranial and intracranial portions of the internal carotid arteries in donkeys. In horses, the extracranial and intracranial pathway of the internal carotid artery has been described. The extracranial pathway of the internal carotid artery begins at the carotid termination and runs on the dorsal surface of the medial compartment of the guttural pouch. Thereafter the internal carotid artery passes through the foramen lacerum to continue intracranially, forming part of the rostrolateral quadrants of the cerebral arterial circle (Circle of Willis). The objectives of this study were to define and record the anatomy of the carotid arterial tree and the internal carotid artery ...
Isolation and characterization of equine native MSC populations. In contrast to humans in which mesenchymal stem/stromal cell (MSC) therapies are still largely in the clinical trial phase, MSCs have been used therapeutically in horses for over 15 years, thus constituting a valuable preclinical model for humans. In human tissues, MSCs have been shown to originate from perivascular cells, namely pericytes and adventitial cells, which are identified by the presence of the cell surface markers CD146 and CD34, respectively. In contrast, the origin of MSCs in equine tissues has not been established, preventing the isolation and culture of defined cell population...
Short-term treatment of equine wounds with orf virus IL-10 and VEGF-E dampens inflammation and promotes repair processes without accelerating closure. Healing is delayed in limb wounds relative to body wounds of horses, partly because of sustained inflammation and inefficient angiogenesis. In laboratory animals, proteins derived from orf virus modulate these processes and enhance healing. We aimed to compare immune cell trafficking and the inflammatory, vascular, and epidermal responses in body and limb wounds of horses and then to investigate the impact of orf virus interleukin-10 and vascular endothelial growth factor-E on these processes. Standardized excisional wounds were created on the body and forelimb of horses and their progression ...
Characterization and angiogenic potential of xenogeneic bone grafting materials: Role of periodontal ligament cells. Adequate revascularization is a prerequisite for successful healing of periodontal bone defects. This study characterized three different xenogeneic bone grafting materials: Gen-Os of equine and porcine origins, and anorganic Bio-Oss. We also investigated their angiogenic potential. All materials were composed of poorly crystalline calcium oxide phosphate, with Bio-Oss exhibiting a carbonated phase and larger particle size and both Gen-Os showing the presence of collagen. Both Gen-Os materials significantly enhanced vascular endothelial growth factor (VEGF) secretion by PDL cells. A significan...
Effect of High-Intensity Training in Normobaric Hypoxia on Thoroughbred Skeletal Muscle. Hypoxic training is believed to increase endurance capacity in association with hypoxia inducible factor-1 (HIF-1), a modulator of vascular endothelial growth factor-A (VEGF-A), and to influence activation of satellite cells (SCs). However, the effect of hypoxic training on SC activation and its relation to angiogenesis has not been thoroughly investigated. Eight Thoroughbred horses were subjected to normoxic (F = 21%) or hypoxic (F = 15%) training for 3 days/week (100% [Formula: see text]) for 4 weeks. Incremental exercise tests (IET) were conducted on a treadmill under normoxia and the ...
Orf virus interleukin-10 and vascular endothelial growth factor-E modulate gene expression in cultured equine dermal fibroblasts. Wounds in horses often exhibit sustained inflammation and inefficient vascularization, leading to excessive fibrosis and clinical complications such as "proud flesh". Orf virus-derived proteins, vascular endothelial growth factor (VEGF)-E and interleukin (ovIL)-10, enhance angiogenesis and control inflammation and fibrosis in skin wounds of laboratory animals. Objective: The study aimed to determine if equine dermal cells respond to VEGF-E and ovIL-10. Equine dermal cells are expected to express VEGF and IL-10 receptors, so viral protein treatment is likely to alter cellular gene expression an...
Attenuation of the blood pressure response to exogenous angiotensin I after oral administration of benazepril to healthy adult horses. Benazepril has been shown to inhibit circulating angiotensin-converting enzyme (ACE) activity in horses but the optimal dosage is unknown. Objective: To determine the lowest tested dose of benazepril that results in ≥75% attenuation in the response of arterial blood pressure (BP) to exogenous angiotensin I (ANG-I) administration. Methods: Prospective experimental study. Methods: A total of 5 healthy horses were instrumented for the direct measurement of BP. Each horse received 4 intragastric doses of benazepril (0.5, 1, 2 and 4 mg/kg bwt) with a washout period of 7 days between doses. Prior ...
The role of relaxin in mare reproductive physiology: A comparative review with other species. Relaxin is a peptide hormone best known for its action during the latter half of pregnancy, in particular for its softening effect on pelvic ligaments that aids in preparation of the birth canal for the impending delivery of the fetus. The source of relaxin during early pregnancy varies across species, with the CL being the main source in a number of species. The main source of relaxin during late equine pregnancy is the placenta. In mares with impaired placental function, circulating relaxin levels decline before abortion. During early pregnancy, relaxin promotes endometrial angiogenesis thro...
Early pregnancy in the mare: old concepts revisited. "Maternal recognition of pregnancy" (MRP) is commonly used to describe the ongoing embryo-maternal communication during early pregnancy that culminates in prevention of luteolysis and ensures ongoing progestin support. The conceptus-derived pregnancy recognition signal has not yet been identified in the mare. Although equine conceptuses produce substantial amounts of estrogens, there is a lack of evidence that estrogens are the pregnancy recognition signal in mares. Conceptus mobility is integral to MRP and is driven by conceptus-derived prostaglandin production. Cessation of conceptus mobilit...
Effect of acute high-intensity exercise in normobaric hypoxia on Thoroughbred skeletal muscle. We examined the effect of transient hypoxic exposure during high-intensity exercise on satellite cell activation and angiogenesis in Thoroughbred skeletal muscle. Methods: Six Thoroughbreds horses (6.3±0.8 years old) ran on a treadmill in normoxia (N; FIO2=21%) and hypoxia (H; FIO2=16%) at the same speed for the same duration, and oxygen consumption and plasma lactate and hemoglobin concentrations were measured. In addition, muscle biopsy samples were obtained from gluteus medius muscle before exercise and immediately, 4 hours, 24 hours, 3 days and 7 days after exercise, and immunohistochemic...
Endoscopic Evaluation of Angiogenesis in the Large Airways of Horses with Heaves Using Narrow Band Imaging. Heaves is a severe debilitating condition of horses, characterized by lower airway inflammation and permanent structural changes of the bronchial wall. Chronic inflammation promotes the formation of new vessels, a phenomenon known as angiogenesis. Narrow band imaging (NBI) endoscopy is a noninvasive technique that enhances the visualization of submucosal vessels, and commonly is employed for the study of angiogenesis in human patients. Objective: Using NBI, we aimed to determine whether or not the central airways of horses with heaves undergo angiogenesis. Methods: Horses with heaves during ex...
The effect of isosorbide dinitrate on uterine and ovarian blood flow in cycling and early pregnant mares: A pilot study. Poor uterine perfusion has been proposed as a cause of infertility in mares. The objective of this study was to investigate the effect of isosorbide dinitrate (ISDN), a nitric oxide donor, on uterine and ovarian blood flow resistance during diestrus and early pregnancy in mares. Six Trotter mares, aged 7 to 14 years, were examined daily during the first 11 days of three diestrous periods, and five of those mares were also examined during the first 11 days of two pregnancies. Six mares randomly received a placebo, a low dose (30 mg, ISDN30), or a high dose of ISDN (60 mg, ISDN60) through t...
Equine endometrial vascular pattern changes during the estrous cycle examined by Narrow Band Imaging hysteroscopy. The aim of this study was to evaluate the uterine blood supply and endometrial vessel architecture, during the equine estrous cycle. Narrow Band Imaging (NBI) hysteroscopy was used for evaluating changes in the endometrial vasculature during the estrous cycle [six mares, d 0 (representing the day of ovulation), d 6 and 11 in four locations]. In addition, endometrial biopsy samples were used for immunodetection of markers for angiogenesis (Vascular Endothelial Growth Factor A, its receptor 2, as well as angiopoietin-2 and its receptor-tyrosine-kinase Tie2) during the estrous cycle (three mares,...
Stimulation of LH, FSH, and luteal blood flow by GnRH during the luteal phase in mares. A study was performed on the effect of a single dose per mare of 0 (n = 9), 100 (n = 8), or 300 (n = 9) of GnRH on Day 10 (Day 0 = ovulation) on concentrations of LH, FSH, and progesterone (P4) and blood flow to the CL ovary. Hormone concentration and blood flow measurements were performed at hours 0 (hour of treatment), 0.25, 0.5, 1, 2, 3, 4, and 6. Blood flow was assessed by spectral Doppler ultrasonography for resistance to blood flow in an ovarian artery before entry into the CL ovary. The percentage of the CL with color Doppler signals of blood flow was estimated from videotapes of real-t...
Effect of activated protein C in second intention healing of equine distal limb wounds: a preliminary study. To investigate the effect of activated protein C (APC) on second intention healing of distal limb wounds in horses. Methods: In this experimental study of eight Standardbred geldings, six full-thickness skin wounds (2 × 1.5 cm) were created on one metacarpus (biopsy limb) and five similar wounds were created on the contralateral metacarpus (photographed limb). Three wounds on the biopsy limb were treated topically with 190 µg APC on days 1, 3, 6 and 9, while the remaining three wounds were untreated (control). One treated and one control wound were biopsied on days 4, 7 and 11 for hi...
Expression of angiogenic factors and luteinizing hormone receptors in the corpus luteum of mares induced to ovulate with deslorelin acetate. The effects of deslorelin acetate use in inducing ovulation need to be clarified to improve the results of equine embryo transfer. The mRNA abundance for angiogenic factors and LH receptor (LHR) in corpus luteum (CL) was studied in mares with natural (control group [CG]) and induced ovulation with deslorelin acetate (treatment group [TG]; follicles: ≥ 35 mm). Transrectal ultrasonography was used to verify the ovulation day, and on Days 4, 8, and 12 after ovulation (Day 0), CL samples were obtained through ultrasound-guided biopsy. The messenger RNA expression of vascular endothelial growth f...
Microangiographic Comparison of the Effects of 3 Loop Pulley and 6 Strand Savage Tenorrhaphy Techniques on Equine Superficial Digital Flexor Tendon. The 6-strand Savage (SSS) tenorrhaphy pattern is biomechanically superior to the commonly employed 3-loop pulley (3LP); however, its effects on intrinsic tendon vasculature remain unknown. The objective of this study was to compare perfusion of intrinsic vasculature of the equine superficial digital flexor tendon (SDFT) after 3LP and SSS tenorrhaphies. We hypothesized that the SSS technique would significantly decrease vascular perfusion compared to the 3LP technique. Methods: Ex vivo, randomized, paired design. Methods: Horses (n = 9) METHODS: Under general anesthesia, 9 pairs of forelimb...
Effects of an anabolic steroid (Durateston) on testicular angiogenesis in peripubertal stallions. The aim of this study was to determine the effect of the anabolic steroid testosterone on the testicular vascularization, angiogenesis and expression of angiogenic factors, and their receptors in testes of peripubertal stallions. Seven peripubertal stallions were treated with Durateston and castrated either 4 (treatment group 1 [TG1]) or 12 weeks (TG2) after the last injection. The castration of seven untreated control stallions (control group [CG]) took place within the same time. In the testicular specimens, volume density (VD), numerical density (ND), and area of vessels were determined mor...
The effects of topical oxygen therapy on equine distal limb dermal wound healing. Topical oxygen therapy (TOT) has been used in human medicine to promote healing in chronic wounds. To test the efficacy and safety of TOT in horses, an experimental wound model was created by making 1 standardized dermal wound on each limb of 4 healthy horses (n = 16). Each wound was fitted with an oxygen delivery cannula and covered with a bandage. One limb of each front and hind pair was randomly assigned to the treatment group (fitted with an oxygen concentrator device), with the contralateral limb assigned to the control group (no device). Wound area, epithelial area, and contraction were ...
Effect of autologous adipose tissue-derived mesenchymal stem cells on neovascularization of artificial equine tendon lesions. To investigate whether autologous adipose tissue-derived mesenchymal stem cells (AT-MSCs) treatment of tendon lesions increases neovascularization during tendon healing. Methods: A standardized surgical model was used to create lesions in both front limb superficial digital flexor tendons (SDFTs) of nine horses. Either AT-MSCs or control substance was injected intralesionally 2 weeks post-surgery. Color Doppler ultrasonography of SDFTs was performed at regular intervals. Horses were euthanized 22 weeks post-treatment and SDFTs were harvested for histology. Results: The color Doppler ultrasonog...
Percutaneous ultrasound-guided arterial angiography for transarterial coil placement in anesthetized and standing horses. To (1) describe ultrasound-guided percutaneous introduction of a transarterial angiographic catheter into the common carotid artery (CCA); (2) investigate the feasibility of using angiography of the carotid arteries in the guttural pouch region and assess transarterial coil (TAC) placement into the internal carotid artery (ICA). Methods: Experimental study. Methods: Healthy Standardbred horses (n = 6), aged 5-8 years. Methods: Six horses had ultrasound-guided percutaneous CCA catheterization and angiography under general anesthesia. Catheterization sites were ultrasonographically evaluated pos...
Peripheral Blood-Derived Mesenchymal Stromal Cells Promote Angiogenesis via Paracrine Stimulation of Vascular Endothelial Growth Factor Secretion in the Equine Model. 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...
Isolation of equine endothelial cells and life cell angiogenesis assay. Arterial or venous thromboses are frequent clinical complications with the risk of fatal progression. Recent studies suggest the disruption of angiogenesis in the course of thrombus resolution as the underlying pathomechanism. Very similar to the situation in human patients, equine vessels have been described to be particularly susceptible to thrombosis. In contrast to humans, equine donors are readily available to obtain organs and tissues for isolation of endothelial cells. Objective of this study was to isolate equine endothelial cells and develop an angiogenesis assay from primary cultures...
Membrane vesicles mediate pro-angiogenic activity of equine adipose-derived mesenchymal stromal cells. Multipotent mesenchymal stromal cells (MSCs) have attracted a great deal of interest, due to several distinctive features, including the ability to migrate to damaged tissue and to participate in tissue regeneration. There is increasing evidence that membrane vesicles (MVs), comprising exosomes and shedding vesicles, represent a key component, responsible for many of the paracrine effects of MSCs. The aim of the present study was to establish whether equine adipose-derived MSCs (E-AdMSCs) produce MVs that are capable of influencing angiogenesis, a key step in tissue regeneration. A morphologic...
Morphometric examination of the equine adult and foal lung. To understand the mechanisms of airway inflammation associated with equine diseases such as Rhodococcus equi infection, we must identify baseline "normal" structural characteristics of the horse lung. To develop a detailed understanding of the morphology of the horse lung, we adapted and applied stereological methods to the lungs from healthy adult horses (N = 4) and 1-day (N = 5) and 30-day (N = 5) old foals. The left lung was fixed in situ by intrabronchial instillation of glutaraldehyde/paraformaldehyde fixative at 25 cm H2 O column and sampled using a fractionator design follow...
Opposing roles of leptin and ghrelin in the equine corpus luteum regulation: an in vitro study. Metabolic hormones have been associated with reproductive function modulation. Thus, the aim of this study was: (i) to characterize the immunolocalization, mRNA and protein levels of leptin (LEP), Ghrelin (GHR) and respective receptors LEPR and Ghr-R1A, throughout luteal phase; and (ii) to evaluate the role of LEP and GHR on progesterone (P4), prostaglandin (PG) E2 and PGF2α , nitric oxide (nitrite), tumor necrosis factor-α (TNF); macrophage migration inhibitory factor (MIF) secretion, and on angiogenic activity (BAEC proliferation), in equine corpus luteum (CL) from early and mid-luteal sta...
Expression and regulation of stromal cell-derived factor-1 (SDF1) and chemokine CXC motif receptor 4 (CXCR4) in equine and bovine preovulatory follicles. The interaction between stromal cell-derived factor-1 (SDF1) and chemokine CXC motif receptor 4 (CXCR4) has been implicated in leukocyte attraction, tissue remodeling and angiogenesis. The objective of the present study was to characterize the expression and regulation of SDF1 and CXCR4 in equine follicles during the ovulatory process. Equine preovulatory follicles were isolated during estrus 0-39h after hCG treatment. Follicle wall preparations (theca interna with attached granulosa cells) and isolated preparations of granulosa cells and theca interna were obtained, and total RNA extracts wer...
Coil embolization of a palatine artery pseudoaneurysm in a gelding. To describe successful transarterial coil embolization of a palatine artery pseudoaneurysm that extended into the caudal maxillary sinus of a gelding. Methods: Clinical report. Methods: A 24-year-old Morgan gelding with right-sided epistaxis. Methods: The right maxillary sinus was imaged by radiography, computed tomography, and sinoscopy. Angiography was performed to locate the source of bleeding, and transarterial coil embolization of a right palatine artery pseudoaneurysm was performed. Results: There was some mucoid nasal discharge and an intermittent cough postoperatively. No epistaxis was...
Microvasculature of the suspensory ligament of the forelimb of horses. To determine the microvascular anatomy of the suspensory ligament of the forelimb of horses. Methods: 17 cadaveric forelimbs from 9 adult horses with no known history of forelimb lameness. Methods: The median artery of the forelimb was cannulated proximal to the antebrachiocarpal joint and injected with contrast medium for CT evaluation of the gross vasculature (n = 2) or India ink to evaluate the microvasculature (12). Routine histologic evaluation was performed on an additional 3 forelimbs to confirm the microvascular anatomy. Results: The vascular supply of the suspensory ligament of the fo...
Equine deep stromal abscesses (51 cases – 2004-2009)–Part 2: the histopathology and immunohistochemical aspect with attention to the histopathologic diagnosis, vascular response, and infectious agents. To investigate histopathologic and immunohistochemical aspects of equine deep stromal abscesses (DSA) with a focus on the histopathologic diagnosis, presumptive etiology, and the immunohistochemical expression of three angiogenesis-related factors: vascular endothelial growth factor-A (VEGF-A), pigment epithelium-derived factor (PEDF), and interleukin-1 receptor antagonist (IL-1ra). Methods: Paraffin-embedded biopsy samples from 51 DSA. The biopsies were collected from full-thickness penetrating keratoplasty or split-thickness lamellar keratoplasty surgeries at the University of Florida Veteri...