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Cyclooxygenase-2 is induced in brain blood vessels during fever evoked by peripheral or central administration of tumor necrosis factor.

Cyclooxygenase-2 (COX-2) is an inducible type of enzyme that is involved in prostaglandin biosynthesis. In the present study, we examined whether or not COX-2 is involved in fever that is induced by tumor necrosis factor-alpha (TNF-alpha) and, if so, where in the brain COX-2 is induced by this factor. Intraperitoneal (i.p.) injection of TNF-alpha into rats evoked a fever that started 1 h after the TNF injection, peaked 3 h after the injection, and then gradually declined. The fever was suppressed by pretreatment with a COX-2-specific inhibitor. With a time course similar to that of fever, COX-2 mRNA was induced in brain blood vessels. On the other hand, in some of the telencephalic neurons, COX-2 mRNA was constitutively expressed under the normal condition; but its level gradually decreased during the course of fever. Fever was also evoked by an intracerebroventricular (i.c.v.) injection of TNF-alpha. This febrile response was also suppressed by a COX-2 specific inhibitor and was associated with the induction of COX-2 mRNA in the brain blood vessels. On the other hand, the telencephalic neurons did not show consistent change in COX-2 mRNA level after i.c.v. injection of TNF-alpha or saline. COX-2-like immunoreactivity was found in some cells of the brain blood vessels 3 h after the TNF-alpha injection by either i.p. or i.c.v. route. Most of the COX-2-like immunoreactive cells were endothelial cells since COX-2-like immunoreactivity was colocalized with von Willebrand factor, an endothelial cell marker, in the same cells. These results suggest that the brain blood vessels are the major sites where TNF-alpha enhances PG biosynthesis after peripheral as well as after central injection, and provides further evidence supporting the hypothesis that COX-2 induced in the brain blood vessels is involved in fever.

Animals↗

Results of treatment of 500 patients with civilian blood vessel trauma.

Results of treatment of 500 patients with blood vessel trauma are analyzed depending on trauma nature, shock severity, regional ischemia, technique of restorative surgery. Biochemical and ultrastructural changes in muscles are described in experimental conditions in ischemia of different degrees of severity to prognosis the reversibility of disorders. Restoration of blood circulation has been achieved in 82% of patients (5.1% mortality). Beside open and closed vessel trauma, it is expedient to distinguish between penetrating and non-penetrating injuries. Results of treatment of blood vessel trauma should be differentiated depending on the degree of regional ischemia, severity of traumatic shock and blood loss, combination of trauma and injury localization. Mechanical suture improves anastomosis quality, simplifies technique and reduces time of intervention. Introduction of microsurgery principles widens possibilities of vessel restorative surgery. The authors suggest classification of iatrogenic injuries of vessels, which promotes accurate diagnosis and choice of optimal surgical technique.

Adult↗

Insulin receptors in calf and human retinal blood vessels.

A system for isolation of capillaries from the retina has been adapted to biochemical studies in vitro. Insulin receptors were identified in human and calf retinal blood vessels. Binding of 125I insulin by calf retinal blood vessels takes place through high affinity (low capacity) and low affinity (high capacity) receptor sites. Insulin binding is inhibited by glucagon, and cGMP and proinsulin. Dissociation of insulin receptor protein or lipid with Triton X-100 or phospholipase results in significant decreases in 125I insulin binding by retinal blood vessels. Dissociation of insulin bound occurs only at 0 degrees C which may be due to rapid internalization of insulin at higher temperatures. Activities of cAMP and cGMP phosphodiesterases and cyclase of retinal vessels were not significantly changed by incubation with insulin. At high concentrations in the media human growth hormone stimulates and then inhibits I125 insulin binding by retinal capillaries.

Aged↗

Cholinesterase activity in the great blood vessels of the heart of Pteropus giganteus.

The great thoracic blood vessels associated with the heart of the Indian flying fox -- Pteropus giganteus were studied histochemically. Acetylcholinesterase was used as a histochemical tool for studying the pattern of distribution of ganglia, nerve plexuses, nerve fibres and nerve endings innervating the various layers of the blood vessels. Their role in the regulation of vasodilation and vasoconstriction is discussed.

Acetylcholinesterase↗

[In vitro differentiation of human bone marrow-derived mesenchymal stem cells into blood vessel endothelial cells].

OBJECTIVE: To study differentiation of human bone marrow-derived mesenchymal stem cells (BDMSC) into blood vessel endothelial cells for ideal cell origin of complex organ tissue engineering vascularization and injured tissue repairing by cell transplantation. METHOD: After different days of induction with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 3D fibrin-gels and matrigel, BDMSC and angiogenesis were determined by the utilization of morphological observation, tissue section and CD34, CD31, vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1), VEGFR-2 (Flk-1), and vWF that were special for blood vessel endothelial cells. RESULT: After 3D-cultured and induced with VEGF and bFGF in vitro in fibrin-gels and matrigel for 3-21 days, BDMSC expressed CD34, CD31, Flt-1, Flk-1, and vWF came into vessel-like configuration. CONCLUSION: VEGF, bFGF as well as Flt-1 and Flk-1, expressed by BDMSC, may form a feasible microenviroment after induction and play an important role during processes of blood vessel endothelial cell differentiation and vessel-like configuration forming of BDMSC. Mesenchymal stem cells may be applied to tissue engineering vascularization and injured tissue repairing by cell transplantation.

Cell Culture Techniques↗

Role of blood vessels in producing pathological changes in the brain with Alzheimer's disease.

Vascular factors have been shown to be highly involved in the deposition of the amyloid beta-protein (A beta) in the brain of Alzheimer's disease (AD). However, the detailed mechanism remains unknown. Here, we showed that more numerous deposits of A beta 40 and A beta 42 in the brain were found in AD patients than in controls. Together with evidence of no difference in the level of A beta 40 and A beta 42 in sera between sporadic AD and controls, a certain dysfunction of the blood-brain barrier could induce an abnormal transport of A beta from sera to the parenchyma in AD. In addition, vascular A beta deposits and mature A beta plaques stained by Congo red in AD brains contained more A beta 40 than A beta 42, whereas Congo red-negative immature plaques mainly consisted of A beta 42. Our confocal laser scanning microscopy demonstrated an intimate relationship between A beta 40 and the vascular network. The amount of mature plaques but not that of immature plaques was reportedly correlated with the severity of dementia in AD patients. These results suggest that serum-derived A beta 40 and/or A beta 42 cause A beta 40 deposition in and around blood vessels through unknown but possible mechanisms such as (1) endocytosis of A beta 40, (2) selective transport A beta 40 and A beta 42 into blood vessels and the parenchyma, respectively, and (3) proteolysis of A beta 42 into A beta 40 induced by a putative carboxyl dipeptidase in blood vessels including vascular feet, which is involved in A beta fibrillation and cognitive deterioration in the patients. Therefore, the accumulation of A beta 40 associated with blood vessels may play a critical role in the development of AD.

Aged↗

Increased expression of endothelin-1 gene in blood vessels of deoxycorticosterone acetate-salt hypertensive rats.

We have recently shown that the content of immunoreactive endothelin-1 is increased in acid extracts from blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats compared with uninephrectomized control rats. We have also found by immunohistochemistry a significant increase in immunoreactive endothelin-1 in endothelial cells of aorta and mesenteric arteries of DOCA-salt hypertensive rats. In the present study, we investigated preproendothelin-1 gene expression in blood vessels of DOCA-salt hypertensive rats and uninephrectomized control rats. Northern blot analysis using a specific 32P-labeled complementary RNA probe for rat preproendothelin-1 of 319 base pairs revealed a fourfold to fivefold increase in abundance of preproendothelin-1 messenger RNA transcripts in both aorta and mesenteric arteries from DOCA-salt hypertensive rats. Thus, increased immunoreactive endothelin-1 content in blood vessels of DOCA-salt hypertensive rats is secondary to increased preproendothelin-1 gene expression. Exaggerated expression of the preproendothelin-1 gene in mineralocorticoid hypertension may contribute to the maintenance of elevated blood pressure.

Animals↗

N(epsilon)-(carboxymethyl)lysine depositions in intramyocardial blood vessels in human and rat acute myocardial infarction: a predictor or reflection of infarction?

OBJECTIVE: Advanced glycation end products (AGEs), such as N(epsilon)-(carboxymethyl)lysine (CML), are implicated in vascular disease. We previously reported increased CML accumulation in small intramyocardial blood vessels in diabetes patients. Diabetes patients have an increased risk for acute myocardial infarction (AMI). Here, we examined a putative relationship between CML and AMI. METHODS AND RESULTS: Heart tissue was stained for CML, myeloperoxidase, and E-selectin in AMI patients (n=26), myocarditis patients (n=17), and control patients (n=15). In AMI patients, CML depositions were 3-fold increased compared with controls in the small intramyocardial blood vessels and predominantly colocalized with activated endothelium (E-selectin-positive) both in infarction and noninfarction areas. A trend of increased CML positivity of the intima of epicardial coronary arteries did not reach significance in AMI patients. In the rat heart AMI model, CML depositions were undetectable after 24 hours of reperfusion, but became clearly visible after 5 days of reperfusion. In line with an inflammatory contribution, human myocarditis was also accompanied by accumulation of CML on the endothelium of intramyocardial blood vessels. CONCLUSIONS: CML, present predominantly on activated endothelium in small intramyocardial blood vessels in patients with AMI, might reflect an increased risk for AMI rather than being a result of AMI.

Aged↗

Effect of pulse rate on collagen deposition in the tissue-engineered blood vessel.

The effect of mechanical stimulation on the development of tissue-engineered blood vessels was examined. In particular, three different rates of radial distension were chosen to produce a nonpulsed environment (0 beats per minute [bpm]), an adult heart rate (90 bpm), and a fetal heart rate (165 bpm). Engineered vessels were cultured for an average of 7 weeks. Vessel walls were then analyzed for collagen content and distribution. In addition, extracellular matrix remodeling was assessed through measurement of active matrix metalloproteinase type 1 (MMP-1) and tissue inhibitor of metalloproteinases type 1 (TIMP-1) levels. Vessels grown at a distension rate of 165 bpm had significantly higher collagen levels than those grown under static conditions. MMP-1 and TIMP-1 levels were also higher under pulsed conditions as compared with nonpulsed conditions. For the 90- and 165-bpm conditions, collagen and MMP-1 levels were not significantly different. TIMP-1 levels were significantly elevated at 165 bpm, indicating an increased cellular response to mechanical stimulation. Mechanical forces and their transduction represent a means to enhance the physical properties of artificial blood vessels, possibly by affecting the rate of extracellular matrix deposition and remodeling.

Animals↗

[Morphofunctional transformations of the blood vessels in the transplantation of syngeneic normal tissue and of a tumor].

In 360 Fisher rats dynamics of changes in blood vessels, the microcirculatory bed vessels included, have been investigated. An original model of the experiment at implantation of syngenic tissues of the fetus normal intestine and tumorous adenocarcinoma of the small intestine has been used. Specific changes of the blood vessels have been revealed around and in the capsule of the implant, depending on their morphological reorganization. The blood vessels changes can serve as a prognostic sign of possible alterations in the implant structure.

Adenocarcinoma↗

The effect of angiogenesis inhibitor TNP-470 on the blood vessels of the lungs, kidneys and livers of treated hamsters.

The growth of solid tumours and their metastases is dependent on the development of new blood vessels (angiogenesis). Therefore angiogenesis inhibitors are potential antitumour drugs. In our previous studies it was found that the angiogenesis inhibitor TNP-470 given to transplantable melanoma-bearing hamsters can decrease the rate of the tumour growth, although the survival time of the animals treated was not significantly affected. It was found finally that TNP-470 given in the vicinity of the growing tumour can cause complete remission of the melanoma in hamsters treated in this way. To check what side-effects could be evoked by such treatment, an examination of the morphology of the blood vessels of the lungs, kidneys and livers of the treated animals was carried out. It was found that the angiogenesis inhibitor applied did not cause any changes which could be observed by light and electron microscopes in the structure of the examined blood vessels of the treated animals.

Angiogenesis Inhibitors↗

Relationship of blood vessels to small intensely fluorescent cells in the autonomic ganglion.

In our experiments we observed the relationship of the blood vessels to the small, intensely fluorescent cells (SIF cells) in the lower mesenteric ganglion of the cat. We injected the solution of Evan's blue into the ganglia and processed them with the fluorescent histochemical method by Falck and Hillarp. We observed that the SIF cells are placed in the ganglia closely to the blood vessels or closely round them. When observing lager groups of SIF cells placed at the edge of the ganglia a dense network of the blood vessels was observed among these cells.

Animals↗

Reduced laminin immunoreactivity in the blood vessel wall of ageing rats correlates with reduced innervation in vivo and following transplantation.

Changes in extracellular matrix composition and/or organization, and in particular in the ratio of axonal growth-promoting components such as laminin to growth-inhibiting molecules, could contribute to the degenerative changes observed in the innervation of some peripheral tissues in old age. We have investigated this issue by evaluating laminin content or accessibility at various locations on blood vessels where we had previously studied age-related alterations in innervation density. We have employed a morphological approach, measuring laminin immunoreactivity by a densitometric application of confocal microscopy, because more conventional biochemical techniques would have been unable to distinguish specific, localized changes in laminin at sites accessible to nerves from heterogeneous changes in other areas of the vessel wall, such as the endothelial basal lamina. We found that in 24-month-old rats laminin immunoreactivity is decreased by 50% at the medial-adventitial border in association with the outer layer of smooth muscle cells, where a parallel decrease is observed in innervation density. Axonal terminals were shown to have access to laminin in this region of the blood vessel wall by double staining with laminin and a general neuronal marker. Changes in laminin immunoreactivity were region-specific on the same blood vessel, thus excluding the possibility of a generalized decrease in immunoreactivity in old age. For example, in the basilar artery intensity of laminin immunoreactivity decreased in old age at the medial-adventitial border, but showed no change in endothelial cell basal lamina and in the adventitia. Moreover, we performed in oculo transplants of blood vessels displaying differences in laminin immunoreactivity and found that the density of innervation correlated with the intensity of laminin staining, thus lending further support to the hypothesis that laminin might play a role in nerve fibre atrophy in old age.

Aging↗

Establishment of heterogeneity among blood vessels: hormone-influenced appearance of hepatic lipase in specific subsets of the ovarian microvasculature.

We used biochemical and structural approaches to analyze the influence of gonadotropic hormones on the association of hepatic lipase with specific subsets of ovarian blood vessels. Western blotting was used to detect this enzyme in effluent collected from heparin-perfused ovaries of nonhormone-treated immature rats and those primed with pregnant mare's serum gonadotropin (PMSG) alone or in combination with human chorionic gonadotropin (hCG). The effects of these hormones on hepatic lipase distribution among ovarian blood vessels was assessed before and after hCG and/or PMSG treatment by immunofluorescence and immunogold cytochemistry. For the latter, immunoreagents and fixative were delivered directly to chilled, unfixed ovaries by in situ vascular perfusion. Data from biochemical and structural analyses indicated that hepatic lipase was absent from nonhormone-treated ovaries. As shown by Western blotting of ovarian effluent, the enzyme appeared following treatment with PMSG and PMSG-hCG; it increased in amount in a time-dependent manner, with a transient decline in the early hours after hCG injection. Enzyme levels paralleled growth and vascularization of follicles and corpora lutea; the fall tended to coincide with early events in luteal angiogenesis. Immunogold microscopy showed that hepatic lipase was abundant in thin-walled blood vessels of theca interna of follicles, corpora lutea, and interstitial cells but sparse in those of the stroma. Moreover, during neovascularization of differentiating corpora lutea, vascular sprouts arising from hepatic lipase-laden thecal vessels appeared to lose, then regain, the enzyme as development progressed. Our findings thus suggest 1) that hormones influence the establishment of endothelial cell heterogeneity within the microvasculature of a single organ and 2) that development of novel endothelial cell properties in specific subsets of blood vessels underlies compartmentalization of function within a tissue.

Animals↗

Effect of the NO scavenger carboxy-ptio on endothelium-dependent vasorelaxation of various blood vessels from rabbits.

In the present study, we investigated the effect of a nitric oxide (NO) scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide [carboxy-PTIO], on endothelium-dependent relaxation of a series of blood vessels from rabbits, such as thoracic aorta and femoral, renal, mesenteric, and pulmonary arteries, using a functional muscle bath technique. Carboxy-PTIO produced concentration-dependent contractions in various vessels. The contractile responses in renal, mesenteric, and pulmonary arteries were significantly greater than those in the aorta and femoral artery. Similarly, phenylephrine-induced contractions in renal, mesenteric, and pulmonary arteries were markedly enhanced after pretreatment with carboxy-PTIO. Also, carboxy-PTIO inhibited acetylcholine-induced relaxation in various blood vessels. The maximum inhibitions in aorta and femoral artery were significantly greater than those in renal, mesenteric, and pulmonary arteries. The present data demonstrate that carboxy-PTIO reduces basal, phenylephrine-, and acetylcholine-induced release of NO in rabbit blood vessels. However, different degrees of inhibition of endothelium-dependent vasorelaxation were observed in various vessels. Specifically, the thoracic aorta and femoral artery are less susceptible to the action of carboxy-PTIO without acetylcholine than renal, mesenteric, and pulmonary arteries. Conversely, the most potent carboxy-PTIO-induced inhibition of acetylcholine-induced vasorelaxation was observed with aorta and femoral arteries. Thus, it is suggested that the contribution of endogenous NO to vascular tone and regional blood flow may vary among different rabbit blood vessels.

Acetylcholine↗

[Early development of cerebral blood vessels: on the morphological changes in endothelial cells during the fetal period in the rat brain].

Developmental changes of cerebral blood vessels in the rat fetal brain from the embryonic day 11 (E 11) to E 21 were chronologically observed with light and electron microscopes. Based on the fine structures the development of the blood vessels was divided into three successive stages: Stage I (from E 11 to E 21). The neural groove fused at the dorsal portion and transferred to the neural tube. Endothelial cells located only around the neural tissue, and showed a primitive nature in their cellular structures, such as immature nucleus and intracytoplasmic organelles. There were many pores at the thin portion of the cytoplasmic processes. Stage II (from E 13 to E 16). Matrix cells in the neural tube began to produce neuroblasts. These neuroblasts migrated from the matrix layer and were recognized as the migrating zone just outside the matrix layer. The formation of the migrating zone started at the ventrolateral portion and successively spread to the lateral neopallium and then to the medial one of the cerebrum. Perineural vessels invaded into the neural tissue at the ventrolateral portion and were distributed in the migrating zone and the matrix layer. It was the first appearance of the intraneural blood vessels, and the next invading seemed to follow the area which formed the migrating zone. The endothelial cells at this stage became to increase their cytoplasmic thickness and simultaneously to protrude many cell processes to the luminal and abluminal sides. Numerous large vesicles in the cytoplasm were also observed. Being associated with the vesicle formation the pores in the cytoplasm were rapidly decreased. Pericytes were recognized around the endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Formation of the branching pattern of blood vessels in the wall of the avian yolk sac studied by a computer simulation.

The present study was performed to provide data to support the notion previously believed but not proved experimentally or theoretically, that blood vessels are formed by the selection of capillaries in the network. In an attempt to understand the mechanism of formation of blood vessel branching structures, the transformation of a capillary network to a branching system in the wall of quail yolk sac was successively recorded by a series of photographs, and a computer simulation was carried out for the process of in vivo vascularization based on the photographs. The simulation demonstrated that a positive feedback system participated in the formation of a branching structure. That is, vessels which had been much used were enlarged, whereas less used vessels were reduced in their size and finally extinguished. The enlarged vessels became major components of the branching system. As the body of an embryo grew, it was observed that polygonal capillary networks enlarged, which led each polygon of the network to divide into a few finer polygons. Then, some of the capillary vessels were again selected and formed a branching system. This process repeated during the body growth, indicating that the vascular system developed adaptively to the body growth. A region where the growth was fast, received much blood flow and produced finer networks of capillaries. Thus, it was experimentally demonstrated for the first time that capillaries in the network are successively selected by a positive feedback mechanism and form blood vessels.

Animals↗

Dose-response relationships for arginine vasopressin and synthetic analogs on three types of rat blood vessels: possible evidence for regional differences in vasopressin receptor sites within a mammal.

These experiments were undertaken to determine the comparative relationships between chemical structure and biologic (contractile) activity of a series of vasopressin hormone analogs on different rat blood vessels (e.g., aorta, mesenteric arteriole and mesenteric venule). The functional contributions to, and interactions with, phenolic hydroxyl and aromatic groups as well as basicity in positions 2, 3 and 8, respectively, to or with hormone-receptor affinity and intrinsic (contractile) activity, were determined by analyzing the dose-response curves of five vasopressin peptides lacking one or more of these functional groups. The findings demonstrate that: 1) the structure-action relationships for vasopressin peptide-induced contractions on rat blood vessels vary with the particular type of macro- or microvessel (i.e., aorta, arteriole and venule); 2) the phenolic and aromatic groups in positions 2 and 3, respectively, are not only important for hormone-receptor affinity but intrinsic activity as well; 3) the potency (EC50) values for arginine vasopressin as well as the potencies and intrinsic activities of synthetic vasopressin analogs varied between the three different types of rat blood vessels examined; and 4) circulating levels (i.e., 10- minus 11- minus 10- minus 12 M) of [8-arginine]-vasopressin are capable of inducing contractile effects on mesenteric arterioles and venules. The quantitative data obtained in this study support the notion that a heterogeneity of the receptor, which subserves contraction, probably exists in blood vessels within and between vascular beds of a single mammalian species.

Amino Acid Sequence↗