SEARCH · PubMed Health

Results for “Microvessels”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources

PubMed1992

Characterization of angiotensin converting enzyme in isolated cerebral microvessels from spontaneously hypertensive and normotensive rats.

OBJECTIVE: Abnormalities in the vascular renin-angiotensin system have been hypothesized to contribute to the pathogenesis and complications of hypertension. In animal models of hypertension, there is wide variation in reported vascular angiotensin converting activity, particularly in cerebral microvessels. In this study, we sought to characterize, quantitate and compare cerebral microvessel angiotensin converting enzyme (ACE) in genetically hypertensive rats and normotensive rats. DESIGN: Brain microvascular ACE from 14-week-old spontaneously hypertensive rats (SHR) was measured and compared with ACE from brain microvessels of normotensive Wistar-Kyoto (WKY) controls. METHODS: Isolated cerebral microvascular ACE was measured using two methods, enzyme kinetic assay or radioligand binding assay. RESULTS: In SHR, cerebral microvessel ACE was of similar activity and concentration and had similar ligand binding affinities to WKY rats. Plasma ACE activity was significantly elevated in WKY rats compared with SHR. CONCLUSION: Cerebral microvascular ACE is similar in SHR and WKY rats. Microvascular ACE is unlikely to participate in the pathogenesis or complications of hypertension in this model.

Animals↗

PubMed1993

Ultrastructural morphometric features of human sural nerve endoneurial microvessels.

We studied the morphometric features of 366 transversely sectioned endoneurial microvessels in sural nerves from 50 healthy volunteers (mean age 34.5 +/- 15.8, range 20 to 66 years). Nerves were obtained and processed by the same techniques and standards used to study biopsied nerves from patients with neuropathy. Endothelial area, basement membrane area, number of endothelial nuclei and junctions, and number of periendothelial nuclei all increase significantly with vessel size as judged by mural area. Periendothelial cell coverage of endothelial perimeter does not correlate with vessel size. Components of endoneurial microvessels, specifically the area containing basement membrane, do not change significantly with age. The present report provides a detailed characterization of the ultrastructural features of endoneurial microvessels with age in humans and provides optimal reference values for study of microvessel pathologic changes in disease.

Adult↗

PubMed1996

Endothelial Gi protein expression is markedly low in human coronary microvessels.

Gi protein functionally mediates endothelium-dependent relaxations in large epicardial coronary arteries but not in small coronary arteries, which suggests a different involvement of Gi protein in the endothelium-dependent relaxations between large and small coronary arteries. We previously showed that endothelial Gi protein is present in human epicardial coronary artery. In the present study, we examined the expression of endothelial Gi protein in human coronary microvessels. Immunohistochemical staining with a specific antibody against human Gi protein was performed in intramyocardial coronary microvessels and vasa vasorum from 34 autopsy cases. The immunoreactive levels of the endothelial Gi protein were semiquantitated into four grades (none, 0; slight, +1; moderate, +2; high, +3), and the mean value of the ratings of all endothelial cells was then used as an index of the endothelial Gi protein expression of the vessel. The immunoreactive levels of the endothelial Gi protein were extremely low in intramyocardial coronary microvessels and in vasa vasorum, irrespective of the age of the patients, the presence or absence of coronary risk factors, or the influence of medical treatments. These results may therefore explain in part why endothelium-dependent relaxations in coronary microvessels are not functionally mediated by Gi protein.

Adolescent↗

PubMed2000

Amlodipine enhances NO production induced by an ACE inhibitor through a kinin-mediated mechanism in canine coronary microvessels.

Our previous study found that angiotensin-converting enzyme (ACE) inhibitors and amlodipine induce NO release from coronary microvessels through a kinin-dependent mechanism. The goal of this study was to determine whether amlodipine could potentiate NO formation during ACE inhibition. Coronary microvessels were isolated from 16 mongrel dogs. Nitrite, the hydration product of NO, from coronary microvessels was quantified by using the Griess reaction. Bradykinin and kallikrein all significantly increased nitrite release from coronary microvessels in a concentration-dependent manner. The ACE inhibitor, ramiprilat, potentiated these effects. Amlodipine also markedly potentiated nitrite production by ramiprilat. For instance, amlodipine (10(-10) M) enhanced nitrite release induced by ramiprilat (10(-7) M) from 122 +/- 9 to 168 +/- 14 pmol/mg (p < 0.05 vs. ramiprilat). Nitrite release potentiated by ramiprilat and amlodipine was entirely blocked by N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase), HOE 140 (Icatibant, a specific B2-kinin receptor antagonist), and dichloroisocoumarin (DCIC, a serine protease inhibitor that blocks local kinin formation). These results clearly show that there is a synergistic effect on NO formation when amlodipine is combined with ACE inhibition. Our data suggest that kinin-mediated coronary NO production may contribute importantly to the beneficial therapeutic action of ACE inhibitors, especially in combination with amlodipine in the treatment of heart disease.

Amlodipine↗

PubMed2003

Cerebral microvessel responses to focal ischemia.

Cerebral microvessels have a unique ultrastructure form, which allows for the close relationship of the endothelium and blood elements to the neurons they serve, via intervening astrocytes. To focal ischemia, the cerebral microvasculature rapidly displays multiple dynamic responses. Immediate events include breakdown of the primary endothelial cell permeability barrier, with transudation of plasma, expression of endothelial cell-leukocyte adhesion receptors, loss of endothelial cell and astrocyte integrin receptors, loss of their matrix ligands, expression of members of several matrix-degrading protease families, and the appearance of receptors associated with angiogenesis and neovascularization. These events occur pari passu with neuron injury. Alterations in the microvessel matrix after the onset of ischemia also suggest links to changes in nonvascular cell viability. Microvascular obstruction within the ischemic territory occurs after occlusion and reperfusion of the feeding arteries ("focal no-reflow" phenomenon). This can result from extrinsic compression and intravascular events, including leukocyte(-platelet) adhesion, platelet-fibrin interactions, and activation of coagulation. All of these events occur in microvessels heterogeneously distributed within the ischemic core. The panorama of acute microvessel responses to focal cerebral ischemia provide opportunities to understand interrelationships between neurons and their microvascular supply and changes that underlie a number of central nervous system neurodegenerative disorders.

Brain Ischemia↗

PubMed2004

Correlation of EPHA2 overexpression with high microvessel count in human primary colorectal cancer.

Evidence suggests that the erythropoietin-producing hepatocellular (EPH) receptor tyrosine kinases (RTKs) and their ephrin (EFN) ligands are involved in human carcinogenesis. Expression of two of them, EFNA1 ligand and its receptor, EPHA2, has been proposed to contribute to tumor-induced neovascularization. Colorectal cancers were examined for expressions of EPHA2 and its ligand EFNA1 by semi-quantitative RT-PCR, and double-immunostained for EPHA2 and CD34. Microvessels in the tumors were counted. Double-staining was also performed in 25 cases of adenoma with focal cancer for comparison. Trends of overexpression of both EPHA2 and EFNA1 was found in tumor tissue compared to the corresponding normal tissue in the same specimen [22/37 (59.5%) and 25/37 (67.5%), respectively; P = 0.100 for EPHA2 and P = 0.009 for EFNA1]. Overexpression of EPHA2 and EFNA1 was noted more frequently in the early stage than in the late stage [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P = 0.007; EFNA1, 15/21 (71.4%) vs. 10/16 (62.5%), P = 0.007]. Both EPHA2 and EFNA1 were more frequently overexpressed in smaller tumors (less than 5 cm) than in larger tumors [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P = 0.017; EFNA1, 16/21 (76.2%) vs. 8/16 (50%), P = 0.001]. Tumors less than 5 cm in diameter and in stages I and II were significantly more likely to overexpress EPHA2 and EFNA1 (P = 0.001 for EPHA2, P = 0.001 for EFNA1). Microvessel counts (MVCs) after immunostaining for CD34 were significantly correlated (r = 0.343, P = 0.037) with overexpression of EPHA2. EPHA2-expressing focal cancer also surrounded microvessels in adenomas with focal cancers. These findings suggest an involvement of EPHA2 in colon carcinogenesis, mainly in stages I and II, and probably through their effect on microvessel induction.

Aged↗

PubMed2005

Assessing microvessels and angiogenesis in human breast cancer, using VE-cadherin.

AIMS: Vascular endothelial (VE)-cadherin, also known as cadherin-5 and CD144, is an adhesion molecule uniquely expressed in endothelial cells. We hypothesized that VE-cadherin may be a useful marker for assessing microvessels and angiogenesis in human breast cancer and sought to determine whether a correlation exists between levels of VE-cadherin, angiogenic markers factor VIII and platelet endothelial cell adhesion molecule (PECAM)-1 and patient outcome in breast cancer. METHODS AND RESULTS: Frozen sections from breast cancer primary tumours (tumour n = 114, background n = 30) were immunostained with VE-cadherin, factor VIII and PECAM-1 antibodies and microvessel number was assessed. RNA was reverse transcribed and analysed by quantitative polymerase chain reaction (Q-PCR). VE-cadherin immunostaining showed a significant difference in microvessel number in tumour compared with background. There was no significant difference in the number of microvessels stained with PECAM-1 or factor VIII; there was increased staining of other structures within the sample and higher general background staining. Q-PCR revealed elevated levels of VE-cadherin and PECAM-1 in tumour samples compared with background tissue and in patients with a poor prognosis, as determined by the Nottingham Prognostic Index. There was no difference in levels with factor VIII. Both VE-cadherin and PECAM-1 had significantly reduced expression in lobular compared with ductal carcinomas: there was no difference with factor VIII. CONCLUSION: Higher levels of angiogenic marker molecules in breast cancer may have an association with poor prognosis in patients. Moreover, VE-cadherin appears to be a preferable marker for such analysis.

Antigens, CD↗

PubMed2005

Microvessel density for melanoma prognosis.

AIMS: Two-hundred and four accessible cases of malignant melanoma from the Grampian region of Scotland, collected over a period of 4 years, were studied for standard prognostic indicators for comparison with microvessel density. METHODS AND RESULTS: The range of tumour thickness varied from in-situ melanoma to 14.8 mm. Microvessel density was assessed using the Chalkley technique on sections immunostained with CD31 antibody to identify endothelium. Vessel counts were performed in the peritumoral host tissue of all specimens. Strong correlation was observed between microvessel density at the tumour edge and tumour thickness (P < 0.001). Multifactorial regression analysis confirms Chalkley estimation as a reliable predictor of the risk of recurrence of melanoma (P < 0.005). The predictive value was found to be superior to the Breslow score, for tumours more than 2 mm thick. CONCLUSIONS: Microvessel assessment of primary melanoma using the Chalkley score technique provides reliable prognostic information on the risk of recurrence of the tumour, particularly for melanomas deeper than 2 mm. It remains to be seen whether this methodology can predict response to novel anti-angiogenic therapies currently entering trials.

Adult↗

PubMed1991

Angiotensin-converting enzyme in macro- and microvessels of the rat.

1. Angiotensin-converting enzyme (ACE) was measured in the aorta, cerebral and mesenteric microvessels of Wistar-Kyoto rats using a specific radioligand assay. 2. Ligand binding studies revealed a four-fold increase in concentration of ACE in mesenteric microvessels, compared with aorta or brain microvessels. The dissociation constant (Kd) was similar in all tissues. 3. The effects of oral administration of the ACE inhibitor S9650 on vascular ACE in vivo were measured. 4. S9650 produced a dose-dependent inhibition of vascular ACE from brain and mesenteric microvessels.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1988

Morphological changes of microvessels in the brain with Alzheimer's disease.

The pathological changes of microvessels in the cerebral cortex in Alzheimer's disease were examined at the ultrastructural level. With transmission electron microscopy (TEM), the endothelial cells of many capillaries and their pericytes exhibited atrophy and swelling with a narrowed lumen. The capillary basal laminas were thickened and tortuous. After isolation of the microvessels by ultrasonic treatment and collagenase digestion, the vascular wall structure was viewed by scanning electron microscopy (SEM). Most of the terminal arterioles had smooth muscle cells with an irregular shape and arrangement and often showed a series of focal constrictions. In some areas, the capillaries were arrayed in a bundle and terminated with tapered ends. Associated with the microvessels were fine filaments which may represent amyloid fibrils. The findings indicate that diffuse atrophy and the deletion of nerve cells in the cerebral cortex might be caused, at least partly, by a circulatory disturbance through the pathomorphologically changed microvessels.

Alzheimer Disease↗

PubMed1983

Identification of muscarinic receptors in rat cerebral cortical microvessels.

Microvessels isolated from rat cerebral cortex consist mainly of capillaries (greater than 85%). Fresh, intact microvessel preparations have been analyzed by radioligand binding techniques for muscarinic receptors. Scatchard analysis of specific quinuclidinyl benzilate (QNB) binding indicates that microvessels possess a large number of muscarinic sites (914 fmol/mg protein) of high affinity (KD = 0.034 nM). The association and dissociation rate constants (0.37 min-1 nM-1 and 0.0067 min-1, respectively) yield an equilibrium KD of 0.018 nM. Displacement of [3H]QNB by muscarinic ligands and control substances is typical of muscarinic receptors. The results indicate that cerebral microvessels possess a large population of muscarinic receptors.

Animals↗

PubMed1984

Angiotensin-converting enzyme activity is reduced in brain microvessels of spontaneously hypertensive rats.

Angiotensin -converting enzyme (ACE) activity in brain microvessels of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) controls was measured. Cerebral microvessels, prepared from the cerebral cortices by the albumin flotation and glass bead filtration technique, were free of neuronal and glial elements. ACE activity in brain microvessels of SHR was lower than that of WKY. A Woolf - Augustinsson -Hofstee plot showed that the reduction of the enzyme activity in SHR was due to a 30% decrease in Vmax, without any change in Km for substrate. The decrease of ACE activity in brain microvessels of SHR may indicate an impairment of the central renin-angiotensin system and may be related to cerebral microvascular dysfunctions occurring in hypertension.

Animals↗

PubMed1985

Alterations of the eicosanoid synthetic capacity of rat brain microvessels following ischemia: relevance to ischemic brain edema.

To know the mechanism underlying ischemic brain edema, a time-course analysis of the eicosanoid synthetic capacity of brain microvessels was carried out using unilateral, middle cerebral artery (MCA)-occluded rats. Concomitant with the development of brain edema the synthetic capacity of all products, including cyclooxygenase and lipoxygenase products, increased significantly. Next the effects of 15-hydroperoxyarachidonic acid (15-HPAA) on the synthetic capacity of microvessels were examined. The drug caused a generalized increase of each product, the profile of which was similar to that obtained with ischemic hemispheres, although the ratios of each product differed somewhat among them. The enhanced synthesis of eicosanoids by 15-HPAA was markedly suppressed by radical scavengers such as alpha-tocopherol, hydroquinone, and 1,2-bis(nicotineamide)-propane. Furthermore, the evolution of brain edema was virtually suppressed by the systemic administration of 1,2-bis(nicotineamide)-propane. The above result suggests that the enzyme activity of the arachidonic acid (AA) cascade of microvessels is stimulated by its own products. Such a mechanism will form a vicious cycle that accelerates the accumulation of free radicals within microvessels and thus may play a role in the progressing disruption of the blood-brain barrier (BBB) following ischemia.

Animals↗

PubMed1985

Low activity of angiotensin-converting enzyme in cerebral microvessels of young spontaneously hypertensive rats.

Angiotensin-converting enzyme (ACE) activity was measured in microvessels prepared from cerebral cortices of 4-week-old spontaneously hypertensive rats (SHR). The Vmax value of the ACE activity in the cerebral microvessels of SHR was lower than that of Wistar Kyoto controls of the same age by 25% without difference in Km value for substrate. The low activity of ACE in the cerebral microvessels of young SHR indicates that in this animal model of hypertension the function of ACE is genetically altered in the cerebral microvessels, which may be correlated with the alteration of the cerebral microcirculation and pathogenesis of hypertension.

Animals↗

PubMed1987

Amyloid angiopathy of Alzheimer's disease: amino acid composition and partial sequence of a 4,200-dalton peptide isolated from cortical microvessels.

The cardinal lesions of Alzheimer's disease are neurofibrillary tangles, senile neuritic plaques, and vascular amyloid, the latter generally involving cortical arteries and small arterioles. All three lesions are composed of amyloid-like, beta-pleated sheet fibrils. Recently, a 4,200-dalton peptide has been isolated from extraparenchymal meningeal vessels, neuritic plaques, and neurofibrillary tangles. The assumption of N-terminal homogeneity in vascular amyloid has been used as an argument for a neuronal (versus blood) origin of the peptide. However, intracortical microvessels from Alzheimer's disease have not been previously isolated. The present studies describe the isolation of a microvessel fraction from Alzheimer's disease and control fresh autopsy human brain. Alzheimer's disease isolated brain microvessels that were extensively laden with amyloid and control microvessels were solubilized in 90% formic acid and analyzed by urea sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The arteriole fraction from the Alzheimer's subject with extensive amyloid angiopathy contained a unique 4,200-dalton peptide, whereas the arterioles or capillaries isolated from two controls and two Alzheimer's disease subjects without angiopathy did not. This peptide was purified by HPLC and amino acid composition analysis showed the peptide is nearly identical to the 4,200-dalton peptide recently isolated from neuritic plaques or from neurofibrillary tangles. Sequence analysis revealed N-terminal heterogeneity. The N-terminal sequence was: Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-Tyr, which is identical to the N-terminal sequence of the 4,200-dalton peptide isolated previously from extraparenchymal meningeal vessels and neuritic plaques.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Gamma-glutamyl transpeptidase activity in brain microvessels exhibits regional heterogeneity.

Brain microvessels form a tight blood-tissue permeability barrier and express high levels of specific enzymes, including gamma-glutamyl transpeptidase (GGTP). This differentiation is thought to be induced by perivascular astrocytes. By using histochemical methods, we found that the percentage of GGTP-positive vessels varied considerably in different areas of rat brain. Enzyme activity was not found in the pineal gland or the median eminence, where the blood-brain barrier is not expressed. In areas where the blood-brain barrier is expressed, the percentage of GGTP-positive vessels varied from 8% in the optic nerve to 100% in the anterior commissure. The neocortex showed a lower percentage of GGTP-positive vessels (2-15%) than anterior olfactory nucleus (42%), subiculum (70%), hippocampus (48%), and striatum (50-58%). Alkaline phosphatase, another brain microvessel-enriched enzyme, did not show these marked regional differences. The morphometric histochemical results were verified by enzymatic assays in homogenates of different regions from rat and bovine brain and in microvessel preparations of bovine putamen and neocortex. During the postnatal development of rat brain, the difference between neocortex and striatum appeared after day 20. The regional heterogeneity of brain microvessels may be caused by astrocytic heterogeneity and reflect regional heterogeneity in microvascular function.

Aging↗

PubMed1993

Altered composition of cerebral microvessel membrane phosphoglycerides from senescent mouse.

Phosphoglyceride and fatty acid composition was determined in the cellular membranes of isolated cerebral microvessels and brain parenchymal cells (neurons and glia) taken from 10-, 20-, and 27-30-month-old C57BL6/NNIA mice. Lipids were extracted from each fraction and the fatty acid profiles of ethanolamine, choline, serine, and inositol phosphoglycerides analyzed by gas chromatography. The results suggest that membrane phosphoglycerides from cerebral microvessels are significantly more affected by the aging process than are those of the brain parenchyma. Relative percentage for fatty acids in cerebral microvessels indicate an overall decline in membrane unsaturation with a concomitant elevation in the level of saturation. The decline in unsaturation is reflected primarily in the loss of precursor fatty acids for arachidonic (18:2n-6 and 20:3n-6) and docosahexaenoic (20:5n-3 and 22:5n-3) acids. Levels of arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids in each phosphoglyceride remained unchanged with age; however, mol% for ethanolamine plasmalogen, a major source of these fatty acids, was significantly reduced in 27-30-month-old mice. Conversely, mol% for choline phosphoglyceride increased with age. The age-related changes in fatty acid profile for microvessel membrane phosphoglycerides are reflected by increased saturation/unsaturation ratios and decreased unsaturation indices. These parameters were not affected by aging in parenchymal membranes.

Aging↗

PubMed2005

Induction of aquaporin 1 but not aquaporin 4 messenger RNA in rat primary brain microvessel endothelial cells in culture.

Aquaporins (AQPs) are a family of proteins that mediate water transport across cells, but the extent to which they are involved in water transport across endothelial cells of the blood-brain barrier is not clear. Expression of AQP1 and AQP4 in rat brain microvessel endothelial cells was investigated in order to determine whether these isoforms were present and, in particular, to examine the hypothesis that brain endothelial expression of AQPs is dynamic and regulated by astrocytic influences. Reverse-transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry showed that AQP1 mRNA and protein are present at very low levels in primary rat brain microvessel endothelial cells, and are up-regulated in passaged cells. Upon passage, endothelial cell expression of mdr1a mRNA is decreased, indicating loss of blood-brain barrier phenotype. In passage 4 endothelial cells, AQP1 mRNA levels are reduced by coculture above rat astrocytes, demonstrating that astrocytic influences are important in maintaining the low levels of AQP1 characteristic of the blood-brain barrier endothelium. Reverse-transcriptase-PCR revealed very low levels of AQP1 mRNA present in the RBE4 rat brain microvessel endothelial cell line, with no expression detected in primary cultures of rat astrocytes or in the C6 rat glioma cell line. In contrast, AQP4 mRNA is strongly expressed in astrocytes, but no expression is found in primary or passaged brain microvessel endothelial cells, or in RBE4 or C6 cells. Our results support the concept that expression of AQP1, which is seen in many non-brain endothelia, is suppressed in the specialized endothelium of the blood-brain barrier.

ATP Binding Cassette Transporter, Subfamily B, Mem↗