Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human endometrium is a mucosa served by a microvascular blood supply that involves benign angiogenesis under the control of ovarian steroids throughout reproductive life. Adrenomedullin is a multifunctional 52-amino acid peptide involved in numerous physiological and pathological processes, including angiogenesis, growth regulation, differentiation, vasodilation and smooth muscle relaxation. We have previously shown that adrenomedullin is present in the human uterus. To investigate further the role of adrenomedullin in human endometrial angiogenesis, a method for the isolation and culture of non-pregnant endometrial endothelium was developed. Enzymatic dispersion and 'Percoll' gradient centrifugation, followed by positive selection using Ulex europaeus agglutinin-coated immunomagnetic beads, yielded pure isolates of endothelium. The cells formed a typical 'cobblestone' monolayer within 5-7 days and expressed the classic endothelial markers, CD31 and von Willebrand factor. The presence of adrenomedullin immunoreactivity in endometrial endothelial cells was shown by immunohistochemistry both in vitro and in vivo. Adrenomedullin promotes growth of endothelial cells as measured by [methyl-(3)H] thymidine uptake. Adrenomedullin also induced cyclic AMP in endometrial endothelial cells. These results demonstrate, for the first time, that adrenomedullin is an autocrine growth factor for human endometrial endothelial cells and is thus involved in endometrial angiogenesis.
Mol Hum Reprod 2000 Sep
PMID:Adrenomedullin is an autocrine regulator of endothelial growth in human endometrium. 1095 53

PECAM-1/CD31 is a cell adhesion and signaling molecule that is enriched at the endothelial cell junctions. Alternative splicing generates multiple PECAM-1 splice variants, which differ in their cytoplasmic domains. It has been suggested that the extracellular ligand-binding property, homophilic versus heterophilic, of these isoforms is controlled by their cytoplasmic tails. To determine whether the cytoplasmic domains also regulate the cell surface distribution of PECAM-1 splice variants, we examined the distribution of CD31-EGFPs (PECAM-1 isoforms tagged with the enhanced green fluorescent protein) in living Chinese hamster ovary cells and in PECAM-1-deficient endothelial cells. Our results indicate that the extracellular, rather than the cytoplasmic domain, directs PECAM-1 to the cell-cell borders. Furthermore, coculturing PECAM-1 expressing and deficient cells along with transfection of CD31-EGFP cDNAs into PECAM-1 deficient cells reveal that this PECAM-1 localization is mediated by homophilic interactions. Although the integrin alphavbeta3 has been shown to interact with PECAM-1, this trans-heterophilic interaction was not detected at the borders of endothelial cells. However, based on cocapping experiments performed on proT cells, we provide evidence that the integrin alphavbeta3 associates with PECAM-1 on the same cell surface as in a cis manner.
Mol Biol Cell 2000 Sep
PMID:PECAM-1/CD31 trans-homophilic binding at the intercellular junctions is independent of its cytoplasmic domain; evidence for heterophilic interaction with integrin alphavbeta3 in Cis. 1098 4

The histogenesis of thyroid gland angiomatoid tumors, probably as a primary angiosarcoma, has been a controversy for many years. These tumors may be variants of undifferentiated (anaplastic) carcinomas. We report a thyroid gland angiomatoid carcinoma in a 61-year-old African American male. The tumor had a heterogeneous pattern with both sarcomatous and epithelioid areas. Tumor cells lined some vascular-like spaces and others had intracytoplasmic lumens containing red blood cells. The tumor cells were found to express multiple endothelial (factor VIII-related antigen, CD31, CD34, and Ulex europaeus I lectin) and epithelial (cytokeratin and epithelial membrane antigen) markers as well as thyroglobulin by immunohistochemistry. This rare presentation demonstrates the heterogeneous nature of thyroid gland angiomatoid carcinoma with both epithelial and endothelial differentiation.
Exp Mol Pathol 2000 Oct
PMID:Immunohistochemical characterization of thyroid gland angiomatoid tumors. 1100 64

Tissue hypoxia has been identified as being a particularly important stimulus for triggering angiogenesis. Here we report early effects of hypoxia/reoxygenation (H/R) on the protein expression profiles and localization patterns of the VEGF and Angiopoietin-Tie systems in adult rat myocardium. Western blot as well as immunohistochemical analyses were performed on hearts obtained from rats exposed to various durations of in vivo systemic hypoxemic hypoxia followed by 24 h reoxygenation. The relative time course of protein expression in response to increasing durations of hypoxia, as indicated from our experiments, seems to suggest the involvement of the VEGF system and the Ang-Tie system in early angiogenesis. An apparent relationship between the expression profiles of Flk-1 and Ang-2 was observed. The most significant and interesting relationship which came to light was the surprisingly coincident yet opposite temporal trends between Ang-1 and Ang-2 protein levels. In the 1 h hypoxia group, there was significant induction of Ang-2 expression (31.3% compared to its baseline control) in contrast to relatively mild Ang-1 expression (23.8% compared to its baseline control). Thereafter Ang-1 displayed a progressive increase in expression, parallel to a progressive decrease in Ang-2 expression, becoming most pronounced in the 4 h hypoxia group (Ang-1, 50% and Ang-2, 12.6% compared to respective baseline control values). This suggests that despite their being antagonists at the receptor level, regulation of Ang-1 and Ang-2 protein levels in response to hypoxia runs much deeper and seems to indicate modulatory control at the transcriptional and/or translational level. Two additional groups of rats were sacrificed 7 days after 4 h hypoxia + 24 h reoxygenation, or after a 28 h period of time-matched normoxia. Left ventricular tissue sections were used to determine capillary density (CD) by using anti-CD31 immunohistochemistry and computer-assisted morphometry. CD was significantly increased in the 4 h hypoxia group compared to control (1814+/-56 vs. 1642+/-43 counts/mm2) confirming that modulation of angiogenic factors and their receptors by H/R is capable of stimulating capillary proliferation in the myocardium. Our study presents the first evidence for the Ang-Tie system's involvement in early stages of myocardial angiogenesis along with the VEGF-Flk-1-Flt-1 system. The stimulation of myocardial angiogenesis by H/R may constitute a potential basis for a possible more long-lived adaptive response to stress afforded by preconditioning stimuli.
Mol Cell Biochem 2000 Oct
PMID:Early effects of hypoxia/reoxygenation on VEGF, ang-1, ang-2 and their receptors in the rat myocardium: implications for myocardial angiogenesis. 1112 53

Although melanin synthesis and the presence of melanosomes are exceptionally reported in nervous system tumors, there is no record of melanotic oligodendrogliomas in the literature. The purpose of the current study was to evaluate whether melanosomes are immunohistochemically and ultrastructurally detectable in nonmelanotic oligodendrogliomas and to verify whether these data are related to prognosis. Thirty surgical specimens (19 primary lesions and 11 recurrences) from 19 patients were examined. Median survival was 80 months. Immunohistochemical studies were performed using the monoclonal antibodies HMB-45, CD31. Mib-1, and p53. Using catalyzed signal amplification (CSA), HMB-45 positivity was noticed in 3 (10%) of the oligodendrogliomas being studied. No correlation with survival was found. Ultrastructural examination displayed the presence of melanosomelike structures. Tumor vascularization, estimated by means of CD31 antibody, was increased in 6 of 19 primary lesions but there was no significant correlation with survival. Nine of the19 primary lesions were p53 negative. In these cases, survival was longer than in p53-positive tumors (P = 0.0213). Proliferation rate, evaluated with Mib-1, was unrelated to survival, but proved greater in recurrences (10 of 11 cases) than in primary tumors (7 of 19 lesions; P = 0.007).
Appl Immunohistochem Mol Morphol 2001 Mar
PMID:Oligodendroglioma: HMB-45 positivity using catalyzed signal amplification method: an immunohistochemical (HMB-45, CD31, p53, Mib-1) and ultrastructural study. 1127 13

Vascular immunotargeting is a mean for a site-selective delivery of drugs and genes to endothelium. In this study, we compared recognition of pulmonary and systemic vessels in rats by candidate carrier monoclonal antibodies (MAbs) to endothelial antigens platelet endothelial cell adhesion molecule (PECAM)-1 (CD31), intercellular adhesion molecule (ICAM)-1 (CD54), Thy-1.1 (CD90.1), angiotensin-converting enzyme (ACE; CD143), and OX-43. Tissue immunostaining showed that endothelial cells were Thy-1.1 positive in capillaries but negative in large vessels. In the lung, anti-ACE MAb provided a positive staining in 100% capillaries vs. 5-20% capillaries in other organs. Other MAbs did not discriminate between pulmonary and systemic vessels. We determined tissue uptake after infusion of 1 microg of (125)I-labeled MAbs in isolated perfused lungs (IPL) or intravenously in intact rats. Uptake in IPL attained 46% of the injected dose (ID) of anti-Thy-1.1 and 20-25% ID of anti-ACE, anti-ICAM-1, and anti-OX-43 (vs. 0.5% ID of control IgG). However, after systemic injection at this dose, only anti-ACE MAb 9B9 displayed selective pulmonary uptake (16 vs. 1% ID/g in other organs). Anti-OX-43 displayed low pulmonary (0.5% ID/g) but significant splenic and cardiac uptake (7 and 2% ID/g). Anti-Thy-1.1 and anti-ICAM-1 displayed moderate pulmonary (4 and 6% ID/g, respectively) and high splenic and hepatic uptake (e.g., 18% ID/g of anti-Thy-1.1 in spleen). The lung-to-blood ratio was 5, 10, and 15 for anti-Thy-1.1, anti-ACE, and anti-ICAM-1, respectively. PECAM antibodies displayed low pulmonary uptake in perfusion (2% ID) and in vivo (3-4% ID/g). However, conjugation with streptavidin (SA) markedly augmented pulmonary uptake of anti-PECAM in perfusion (10-54% ID, depending on an antibody clone) and in vivo (up to 15% ID/g). Therefore, ACE-, Thy-1.1-, ICAM-1-, and SA-conjugated PECAM MAbs are candidate carriers for pulmonary targeting. ACE MAb offers a high selectivity of pulmonary targeting in vivo, likely because of a high content of ACE-positive capillaries in the lungs.
Am J Physiol Lung Cell Mol Physiol 2001 Jun
PMID:Lung uptake of antibodies to endothelial antigens: key determinants of vascular immunotargeting. 1135 Aug 15

Coronary microvascular endothelial cells exert (patho)physiological effects on the function of cardiac myocytes, which may be studied experimentally using pure cell populations. As an essential pre-requisite to the investigation of cells from gene-modified mice, we studied the phenotypic properties of coronary microvascular endothelial cells isolated from normal mice, and biochemically characterized the superoxide production by these cells. Microvascular endothelial cells were isolated from devitalized mouse ventricular tissue after sequential digestion with collagenase, trypsin and DNase. Coronary microvascular endothelial cells were separated from cardiac myocytes and other cells by differential centrifugation, plating and culture. Mouse coronary microvascular endothelial cells showed an irregular "cobblestone" morphology at confluence, were >98% positive for CD31 by FACS analysis, and were also positive for VE-cadherin and endothelial-type nitric oxide synthase (eNOS) by confocal microscopy. The cells took up fluorescently labelled, acetylated low-density lipoprotein, but were negative for a alpha -smooth muscle actin, desmin and cytokeratin. Unlike human endothelial cells, mouse coronary microvascular endothelial cells only weakly expressed von Willebrand factor. Immunoblotting showed that the mouse cells expressed components of a phagocyte-type NADPH oxidase. They exhibited NADPH-dependent O(2)(-)-generating activity, which was increased by angiotensin II but completely inhibited by diphenyleneiodonium. Thus, mouse coronary microvascular endothelial cells express both eNOS and NADPH oxidase, interactions between which may play a role in endothelial cell pathophysiology.
J Mol Cell Cardiol 2001 Jun
PMID:Phenotypic properties and characteristics of superoxide production by mouse coronary microvascular endothelial cells. 1144 17

Adhesion molecules on endothelial cells are known to be important ligands for malaria infected red blood cells (PRBC) [Mol Biochem Parasitol, 76, (1996) 1], and may be involved in the pathogenic process of cerebral malaria (CM) which is the most serious complication of falciparum malaria, through enhancing micro embolism or sequestration in the capillaries of the brain. PECAM-1/CD31 is one of these candidate ligands and is coded by a polymorphic gene. Two hundred and ten Thai malaria patients (43 cerebral, 89 severe and 78 uncomplicated) were analyzed for their genetic polymorphism of CD31 to examine the clinical relationship between the disease and specific genotypes. Four alleles were defined 125 valine (V)-563 asparagine (N); 125V-563 serine (S); 125 leucine (L)-563N; and 125L-563S. We found that the frequency of the 125 V/V 563 N/N genotype was significantly high in CM patients as compared with severe cases without CM (P<0.01, OR=2.92), suggesting that this genotype is one of the risk factors for CM.
 ...
PMID:Association of adhesion molecule PECAM-1/CD31 polymorphism with susceptibility to cerebral malaria in Thais. 1171 9

Partial outlet obstruction of the rabbit urinary bladder results, initially, in a rapid increase in bladder mass and remodeling of the bladder wall. Previously, it was shown that this response was characterized by serosal growth (thickening) which was apparent after 1 day of obstruction, before any visible vascularization was observed. After 1 week of obstruction, significant microvessel formation was seen in the transition region between the detrusor smooth muscle and the thickening serosa; after 2 weeks the entire serosa was vascularized. In this study we investigated the effect of chronic (4 week) partial outlet obstruction on microvessel density and distribution in the bladder wall immunohistochemically using CD31 as a marker for vascular endothelium. Transverse sections of bladder wall were examined after 4 weeks of no surgery, sham surgery or partial obstruction. The microvessel density of the obstructed rabbit bladder mucosa and detrusor smooth muscle increased relative to augmentation of these compartments while new vessels appeared in the thickening serosa. Although vessel density did not change with obstruction a significant shift in mean vessel circumference to the left occurred indicating a significant increase in the number of microvessels and small vessels consistent with angiogenesis.
Mol Cell Biochem 2001 Oct
PMID:Vascular response of the rabbit bladder to chronic partial outlet obstruction. 1176 30

This report describes a case of pulmonary epithelioid haemangioendothelioma in which the tumour cells expressed the glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase. The patient, a 15 year old girl, who had no other complaints or past illnesses, was found to have an abnormal shadow on a chest roentgenogram obtained at a school medical examination. Multiple nodular shadows in the bilateral lungs were also confirmed by computerised axial tomography scan. A diagnosis of pulmonary epithelioid haemangioendothelioma was made on the basis of lung biopsy specimens. The tumour cells were immunohistochemically positive for factor VIII related antigen, CD31, and CD34, but not surfactant apoprotein A. In addition, almost all of the tumour cells showed simultaneous expression of the glucocorticoid receptor and 11beta hydroxysteroid dehydrogenase, suggesting that steroid treatment would be effective.
Mol Pathol 2002 Feb
PMID:Expression of glucocorticoid receptor and 11beta hydroxysteroid dehydrogenase in a case of pulmonary epithelioid haemangioendothelioma. 1183 50


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