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A role for axon guidance receptors and ligands in blood vessel development and tumor angiogenesis.

Nerves and blood vessels resemble each other in their ability to form branching networks. They are in close proximity suggesting possible molecular interactions. The patterning of nerves and blood vessels are not random but are regulated by attractive and repulsive cues. Four major neuronal guidance factors that are sensed by growth cones have been identified, Semaphorin, Ephrin, Slit and Netrin, and their cognate receptors, neuropilin, Eph, roundabouts (Robo) and uncoordinated-5 (UNC5). Unexpectedly, these ligand/receptor pairs also regulate developmental and tumor angiogenesis. Together, there is strong evidence that development of the nervous and vascular systems are regulated by common cues.

Axons↗

Injuries to Major Blood Vessels During Laparoscopy

Major blood vessel injury is a true emergency during laparoscopic procedures. Too often, the act or fear of litigation quashes the opportunity to assess the cause and learn from the experience of others. Frequently, only through a medicolegal review can such events be evaluated. After reviewing 40 such cases, the following lessons were learned. Proper technique when inserting the Veress needle, laparoscopic cannulas, and open cannulas can prevent most such accidents. If the standard precautions during insertion are breached, safety shields on disposable cannula sleeves do not prevent or reduce the risk of major vessel injury. Retroperitoneal hematomas require exploratory laparotomy for proper assessment. Distorted anatomy or steep Trendelenburg position may increase the risk of vessel injury. Dissections around the great vessels of the pelvis require the same methods and precautions as with laparotomy.

Journal Article↗

Regulation by angiotensin II of its receptors in resistance blood vessels.

The sensitivity of blood vessels to the vasoconstrictor effects of the hormone angiotensin II appears to be modulated by the activity of the renin-angiotensin system. Elevation of circulating angiotensin II levels by sodium depletion or renal artery stenosis is associated with a diminished pressor response to infused angiotensin II (refs 1-3). Conversely, the vasocontrictor response to the hormone is enhanced when endogenous angiotensin II levels are reduced by sodium loading or nephrectomy. The mechanisms of these varying effects are not known, but physiological and pharmacological experiments suggest involvement of the vascular smooth receptor for angiotensin II (refs 5-8). Modification of the interaction between angiotensin II and its vascular receptor, resulting in altered responsiveness to the hormone, could occur either via 'prior occupancy' of receptors by elevated levels of endogenous angiotensin II resulting in fewer free receptors available to respond to circulating angiotensin II (ref. 5), or, elevated levels of angiotensin II could result in a decrease in receptor affinity for the hormone or a decrease in total receptor number in the vascular smooth muscle cell. We now report the first direct evidence, by radioligand binding assay, that angiotensin II regulates the number of its own receptors in resistance vasculature.

Angiotensin II↗

Vascularization of normal and neoplastic tissues grafted to the chick chorioallantois. Role of host and preexisting graft blood vessels.

Adult, embryonic, and tumor tissues were grafted to the chorioallantoic membrane of the chick embryo to determine whether blood vessels originally within implants were reused in the establishment of a new blood supply. Grafts were examined daily by in vivo stereomicroscopy and in histologic sections. Colloidal carbon injections into the host vasculature served to confirm the precise onset of graft circulation; Preexisting tumor blood vessels disintegrated by 24 hours after implantation and revascularization occurred at 3 days by penetration of proliferating host vessels into the tumor tissue. Adult tissues did not revascularize, and the original graft vasculature progressively disintegrated during the 9 days of observation, Most embryonic tissues revascularized in 1 or 2 days by reperfusion of the existing graft vasculature. Anastomosis of host and graft blood vessels seemed to result from connections between newly formed vascular sprouts arising from both vasculatures. This study indicates that only tumor grafts acquire their blood supply solely by formation of new blood vessels from the host microvasculature. By contrast revascularization of normal tissues, when it does occur, is predominately the result of perfusion of the preexisting graft blood vessels.

Allantois↗

Molecular mechanisms of blood vessel formation.

The formation of new blood vessels, angiogenesis, is a tightly regulated process. Extracellular angiogenic inducers stimulate the migration and proliferation of endothelial cells, while negative regulators counteract this effect. Changes in the relative balance of inducers and inhibitors activate the 'angiogenic switch', before stabilizer molecules activate the maturation of nascent blood vessels.

Angiostatins↗

[Role of perivascular phagocyte (FGP) of cerebral small blood vessel in cerebral edema].

Small cerebral blood vessels are provided with slender phagocytic cells which were designated as FGP (fluorescent granular perithelial) cells from their localization and property. They were derived from pial cells and became potent in the uptake capacity for exogenous substance about at one week after birth. The present study aims to confirm the role of FGP cells and to clarify morphological changes of them in cerebral edema. Cerebral cortices of Wistar rats received head injury (caused with dry ice) were studied electron microscopically at 0.5, 2, 5, 10, 16, 30, 48 and 72 hours after the injury. At the same interval, HRP (horseradish peroxidase) was injected intravenously for the demonstration of uptake capacity of FGP cells. The authors' attention focused on the change of ultrastructure of vascular wall including perivascular phagocytic FGP cell around small blood vessels and on the uptake capacity of FGP cells at each time. From 2 to 5 hours after the cold injury, pinocytotic vesicles often appeared in endothelium and smooth muscle cells, and blood plasma infiltrated into the perivascular space and was taken in the FGP cells. The FGP cells in control were provided with intense round inclusion bodies and looked moderately intense. However, the FGP cells in the experimental animals after the injury became swollen and vacuolized following the fusion of inclusion bodies and breakdown of their limiting membrane and looked pale owing to presence of vacuoles. Under this condition, the uptake capacity of FGP cells for HRP decreased remarkably, and ACPase which was confined to the inclusion bodies in controls spread diffusely into cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The blood vessel system in the periodontal ligament of the equine cheek teeth--part I: The spatial arrangement in layers.

Corrosion casts of blood vessels in the periodontium of cheek teeth from eight horses were observed three-dimensionally with a dissection microscope. Selected specimens were examined in a scanning electron microscope. Periodontal blood vessels communicated with those from the gingiva, the alveolar bone, and the apical region. In the upper jaw, there were anastomoses with the blood vessels of the mucosa of the maxillary sinus. The periodontal vascular system was organized in two or three layers. The peripheral layer was mainly composed of large venules, the inner one consisted of capillaries. In the intermediate layer, blood vessels were post-capillary venules. This layer was developed only in horses under 10 years of age. In all layers the vascular orientation was mainly occluso-apical, this was defined as the standard pattern. There were many variations displayed in different courses of certain blood vessels. The vascular organization is discussed with regard to the specialized functions of the periodontal ligament (PDL). The wide vessels of the outer layer are thought to play a mechanical role as part of a shock absorbing system. The capillaries of the inner layer meet nutritional requirements. The disappearance of the intermediate layer in horses older than 10 years is taken as an adaptation to the remodelling of the PDL. Modifications in the standard pattern of vascular arrangements are also interpreted as adaptations to life-long changes in the periodontal space. Anastomoses between the periodontal vasculature and the blood vessels of the maxillary sinus indicate that periodontal disease may be transferred into the sinus.

Animals↗

Hemodynamic parameters and early intimal thickening in branching blood vessels.

Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in medium to large blood vessels is a major contributor to heart disease, the leading cause of death in the Western World. Balloon angioplasty with stenting, bypass surgery, and endarterectomy (with or without patch reconstruction) are some of the techniques currently applied to occluded blood vessels. On the basis of the preponderance of clinical evidence that disturbed flow patterns play a key role in the onset and progression of atherosclerosis and intimal hyperplasia, it is of interest to analyze suitable hemodynamic wall parameters that indicate susceptible sites of intimal thickening and/or favorable conditions for thrombi formation. These parameters, based on the wall shear stress, wall pressure, or particle deposition, are applied to interpret experimental/clinical observations of intimal thickening. Utilizing the parameters as "indicator" functions, internal branching blood vessel geometries are analyzed and possibly altered for different purposes: early detection of possibly highly stenosed vessel segments, prediction of future disease progression, and vessel redesign to potentially improve long-term patency rates. At the present time, the focus is on the identification of susceptible sites in branching blood vessels and their subsequent redesign, employing hemodynamic wall parameters. Specifically, the time-averaged wall shear stress (WSS), its spatial gradient (WSSG), the oscillatory shear index (OSI), and the wall shear stress angle gradient (WSSAG) are compared with experimental data for an aortoceliac junction. Then, the OSI, wall particle density (WPD), and WSSAG are segmentally averaged for different carotid artery bifurcations and compared with clinical data of intimal thickening. The third branching blood vessel under consideration is the graft-to-vein anastomosis of a vascular access graft. Suggested redesigns reduce several hemodynamic parameters (i.e., the WSSG, WSSAG, and normal pressure gradient [NPG]), thereby reducing the likelihood of restenosis, especially near the critical toe region.

Animals↗

[Primary experimental study on the construction of tissue engineering blood vessel].

OBJECTIVE: To explore the primary experimental methods to construct tissue engineering blood vessel. METHODS: Using the collagen-chitosan to prefabricate the scaffolds with 3-dimensional structure, the proliferated human endothelial cells (ECs), smooth muscle cells (SMCs) and fibroblasts act as the seed cells. The cells were seeded to scaffolds in two-step method, and engineering tissue were matured by static culture or bioreactor culture. Extracellular matrix contents and the platelet aggregation were examined in engineering tissue, tissue engineering blood vessels were taken as patches to repair the man-made defaults on the rats aorta. RESULTS: The proliferated human ECs, SMCs and fibroblast can hold activity and act as seed cells. The prefabricated scaffolds, with excellently cell and tissue biocompatibility, can facilitated cells adherence and upgrowth, the cells quantities and extracellular matrix contents in engineered tissue are time dependent increase (P < 0.05). Platelet aggregation tests confirm the tissue engineering blood vessel have some anti-coagulability. Using the engineering tissue patch to repair the default, 6 aortas in 8 animal were patency till 10 days post-operation. CONCLUSIONS: The seeding cells can be seeded on the 3-dimensional collagen-chitosan scaffolds and matured, the tissue engineering blood vessel can be constructed primarily.

Animals↗

Mechanism of IL-12 mediated alterations in tumour blood vessel morphology: analysis using whole-tissue mounts.

New blood vessel formation within tumours is a critical feature for tumour growth. A major limitation in understanding this complex process has been the inability to visualise and analyse vessel formation. Here, we report on the development of a whole-tissue mount technique that allows visualisation of vessel structure. Mice expressing green fluorescent protein (GFP) made it possible to easily see GFP(+) vessels within non-GFP-expressing B16 melanoma tumours. The small fragments of tumour used in this technique were also effectively stained with fluorescent probe-conjugated antibodies, allowing characterisation of the vessels based on surface marker phenotype. The vessels within tumour tissue were much more irregular and tortuous compared to those within surrounding normal muscle. B16 tumours stably transfected with the genes for IL-12 were used to assess the effects of this cytokine on tumour growth and vessel formation. The IL-12-expressing tumours grew more slowly and had much smaller blood vessels than the large, webbed vessels characteristic of the parental tumours, effects that were dependent on interferon gamma (IFN-gamma). Vessels in the parental tumours were found to express VEGFR-3, the receptor for VEGF-C and VEGF-D. Expression of this receptor by the endothelial cells of the blood vessels was lost in the cytokine expressing tumours, thus suggesting a mechanism for the antiangiogenic effects of IL-12. The combination of the whole mount technique and the GFP transgenic mice provides a powerful method for visualising tumour vasculature and characterising the effects of agents such as cytokines.

Animals↗

A three-dimensional analysis of blood vessels in bronchioloalveolar carcinoma.

The three-dimensional architecture of blood vessels within lung adenocarcinomas has not been well studied. In 19 cases with bronchioloalveolar carcinoma with central fibrosis, we three-dimensionally examined blood vessel architecture in 150 microm thick sections stained with elastin staining and anti-CD34 antibody. We examined four regions: normal alveoli and three regions within the tumor including an area adjacent to the normal alveoli (external area), an area in which tumor cells were replacing epithelial cells (replacement area), and a central fibrotic area (fibrotic area). Elastin staining showed that elastic fibers formed the framework of the alveoli, and the alveolar structure shrank more strongly to the center of the tumor due to folding of alveolar walls invaded by adenocarcinoma cells. We also measured three vessel parameters in these four regions. The vessel diameters were 4.08+/-1.10 microm, 3.95+/-1.02 microm, 5.04+/-1.56 microm, and 6.11+/-2.23 microm, the circumferences of those vessels seen as complete circles were 43.11+/-12.78 microm, 43.71+/-12.87 microm, 95.21+/-39.32 microm, and 126.77+/-54.65 microm; the lengths between vessel bifurcations were 13.28+/-3.08 microm, 13.47+/-4.58 microm, 24.91+/-9.66 microm, and 41.82+/-28.08 microm in the normal alveoli, and the external, replacement, and fibrotic areas, respectively. Blood vessel architecture changed such that the vessels became larger and coarser towards the center of the tumor. Our three-dimensional analysis suggests continuous remodeling of alveolar capillaries rather than angiogenesis within bronchioloalveolar carcinoma.

Adenocarcinoma, Bronchiolo-Alveolar↗

Ultrastructural study on the small blood vessels of human vocal cords.

Small blood vessels of human vocal cords were examined by electron microscopy. The endothelial cells contain a large number of filaments. Two kinds of filaments could be differentiated: Short intermediate filaments with a diameter of 10-12 nm, which were localized in the pericaryon, and bundles of thin filaments with a periodicity of 480 nm lying beneath the luminal cellular membrane. The basement membrane of capillaries, arteries, and veins was lamellate. Between the outermost, not fully closed lamellae, myocytes or pericytes could be seen. Both the lamellate basement membranes and the large number of intermediate filaments in the endothelial cells are discussed as stabilizing structures in blood vessels which are exposed to high mechanical forces. The bundles of cross-striated thin filaments may possibly increase the permeability of the vessel wall by their contraction, permitting the well-known fast development of edema in the vocal cords. The importance of Weibel-Palade bodies, which could be disclosed in the endothelial cells in large numbers, is not yet known.

Capillaries↗

[Treatment techniques of harvesting injury of donor renal blood vessels].

OBJECTIVE: To study the treatment technique for harvesting injury of donor blood vessels for the clinic application. METHODS: The data of 32 renal transplantation patients with injury of graft blood vessels were retrospectively reviewed. 60 renal transplantation patients with non-injury during the same term were selected as the control group. The treatment techniques for harvesting injury of graft blood vessels mainly includes end-to-end anastomosis of graft artery, side-to-side anastomosis of branch artery, end-to-side anastomosis of branch artery to the main renal artery, reconstruction of multiple segmental arteries by using iliac arterial grafts from cadaveric donors or recipients on the workbench, repairs of injuries for the smaller segmental/polar arteries by using inferior epigastric artery, end-to-end anastomosis of the lower thick segmental/polar arteries with the iliac internal arterial by placing kidney upside down. RESULTS: Those injured included 28 arterial and 4 venous. Average bench surgery time was 42 minutes. Mean warm ischemic time was 31 minutes. No death occurred at an average follow-up of 3.5 years (1 - 5 years). There was no statistical difference in the 1-year graft survival, postoperative 1-year acute rejection, delayed graft function (DGF) and the incidence of constriction of vascular anastomosis rate (96.9%, 12.5%, 21.9%, 3.1%, respectively) compared with non-reconstructed kidneys during the same term (98.3%, 11.7%, 18.3%, 1.7%, P > 0.05, respectively). CONCLUSION: The flexible and appropriate application of different vascular reconstruction means and satisfactory surgery techniques play an important role in assuring quality of kidney with harvesting blood vessels injury and donor kidney availability.

Adolescent↗

[The formation of new blood vessels in coronary artery disease: where we are now].

New blood vessel formation is of great importance to clinicians and researchers because of its participation in many diseases. Scientists are trying to exploit the mechanisms of vasculogenesis, angiogenesis, and arteriogenesis in the treatment of coronary artery disease. These mechanisms are employed to improve myocardium vascularization in patients where both pharmacological therapy and available revascularization procedures (PTCA, CABG) are not effective. In such cases, factors including vascular endothelial growth factor (VEGF), acid fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), granulocyte/macrophage colony-stimulating factor (GM-CSF), and granulocyte colony stimulating factor (G-CSF), as well as stem cells, have been applied so far. This article is a review of the current knowledge about new blood vessel formation, especially in ischemic myocardium. We have also analyzed alternative strategies of treating coronary artery disease using the mechanisms of angiogenesis, arteriogenesis, and vasculogenesis.

Angioplasty, Balloon, Coronary↗

[Early development of cerebral blood vessels: on the relationship between cerebral histogenesis and internal vascularization].

The purpose of this study is to evaluate the morphological relevance to cerebral histogenesis and internal vascularization during early fetal development of rats. Using light and electron microscopes, fetal brains and spinal cords from embryonic day 11 (E11) to E 16 were observed with special attention to new blood vessel formation in the parenchyma. At stages of the neural groove and neural tube blood vessels were confined in the perineural mesenchyma around the matrix cell layer whose cytoarchitecture was arranged in a pseudostratified pattern and did not include the blood vessels. At the prosencephalic stage (E 13), primordium of the striatum which localized in the ventrolateral portion of the cerebral neopallium made up the migrating zone in outer most of the matrix cell layer and blood vessels firstly appeared in this area. Similarly, the blood vessels were also recognized at the ventro-lateral portion of the mesencephalon where the migrating zone was initially formed on E 13. In the cervical spinal cord, the blood vessels were initially recognized on E 12, when the migrating zone was formed at the area of anterior horn. At the early telencephalic stage during E 14-E 15, blood vessels were evenly distributed in the lateral cerebral neopallium, while the cerebral neopallium in the midline where took place later evolution than lateral neopallium was still remaining in the state of matrix cell layer only, and was also lacking the blood vessels. In this area, first appearance of the vessels was E 15 or E 16.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of pulsatile flow pattern and each stage of pressure increasing, constant and decreasing, respectively upon inelastic deformation of blood vessel.

The aim of this study is to elucidate the relation of the inelastic expansive deformation of natural blood vessel and the degradation of elasticity to the time pattern of circulating pulsatile pressure flow. When pulsatile pressure amplitude (delta P = Pmax - Pmin) becomes smaller due to Pmin increasing, the blood vessel is subject to creep deformation. In this sense, pulsating pressure will play a role in avoiding creep effect. Fluctuation of maximum pressure Pmax will induce the increase of inelastic deformation and the decrease of rigidity of the blood vessel. The inelastic deformation and the decrease of rigidity in blood vessel is induced at the stage of pressure amplitude rising from a lower one to a higher, but not during pressure amplitude (delta P) kept constant nor at the pressure amplitude decreasing stage. In order to reduce the degradation of mechanical properties of blood vessel, it may be effective to avoid the increase of Pmin and the variability of Pmax.

Biomechanical Phenomena↗

Stereographic demonstration of the nasal cavity of the rat with reference to the density of blood vessels.

Stereographic demonstration of the nasal cavity and distribution of the density of blood vessels were analyzed by computer simulation of serial sections of the rat nose. The nasal cavity was lined by 3 types of epithelium: Stratified epithelium covering the nasal vestibule, the anterior part of the maxilloturbinale, and the anterior part of the septum; respiratory epithelium covering most of the naso- and maxilloturbinalia, and middle part of the septum; and olfactory epithelium covering most of the ethmoturbinale and postero-dorsal part of the septum. Distribution of densities of blood vessels in the lamina propria of the nasal mucosa was roughly correlated with the distribution of the 3 types of epithelium: 194 blood vessels/mm2 of lamina propria beneath the olfactory epithelium; 82 vessels/mm2 beneath the stratified epithelium; and 66 vessels/mm2 beneath the respiratory epithelium. The average density of blood vessels in the nasal cavity was 3.8 times higher than that of the oral cavity. The high density of blood vessels in the nasal cavity was considered to be related to the function of the nose, i.e., the warming and humidification of inspired air.

Animals↗

A completely biological tissue-engineered human blood vessel.

Mechanically challenged tissue-engineered organs, such as blood vessels, traditionally relied on synthetic or modified biological materials for structural support. In this report, we present a novel approach to tissue-engineered blood vessel (TEBV) production that is based exclusively on the use of cultured human cells, i.e., without any synthetic or exogenous biomaterials. Human vascular smooth muscle cells (SMC) cultured with ascorbic acid produced a cohesive cellular sheet. This sheet was placed around a tubular support to produce the media of the vessel. A similar sheet of human fibroblasts was wrapped around the media to provide the adventitia. After maturation, the tubular support was removed and endothelial cells were seeded in the lumen. This TEBV featured a well-defined, three-layered organization and numerous extracellular matrix proteins, including elastin. In this environment, SMC reexpressed desmin, a differentiation marker known to be lost under standard culture conditions. The endothelium expressed von Willebrand factor, incorporated acetylated LDL, produced PGI2, and strongly inhibited platelet adhesion in vitro. The complete vessel had a burst strength over 2000 mmHg. This is the first completely biological TEBV to display a burst strength comparable to that of human vessels. Short-term grafting experiment in a canine model demonstrated good handling and suturability characteristics. Taken together, these results suggest that this novel technique can produce completely biological vessels fulfilling the fundamental requirements for grafting: high burst strength, positive surgical handling, and a functional endothelium.

Animals↗