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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino-acid homocysteine plays a crucial role in cell metabolism. It participates in the remethylation pathway enabling maintenance of adequate cellular levels of methionine or is catabolized by transsulphuration. A number of hereditary defects in the enzymes involved in homocysteine metabolism and acquired deficiencies in the vitamin cofactors of these enzymes are associated with the development of hyperhomocysteinaemia. The association between high circulating homocysteine levels and premature vascular thrombosis is well established in individuals with hereditary homocystinuria. There is now good epidemiological evidence that mild hyperhomocysteinaemia is an independent risk factor in the development of arterial disease and venous thrombosis although the causes of the elevated plasma homocysteine are unclear. A good candidate is homozygosity for the common thermolabile variant of methylenetetrahydrofolate reductase but the evidence for a causative association is conflicting. A number of in vitro effects of homocysteine on vascular endothelium, platelets and coagulation have been described which may predispose to vascular disease but the exact in vivo mechanisms remain to be elucidated. Dietary folate supplementation may normalize homocysteine in hyperhomocysteinaemic individuals and modify the risk of vascular disease.
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PMID:Hyperhomocysteinaemia and vascular disease. 959 95

Hyperhomocysteinemia is an independent risk factor for atherothrombotic disease. The mechanism by which homocysteine induces atherosclerosis and thrombosis is not fully understood. Data on arterial histology in humans with homocystinuria and mild hyperhomocysteinemia are limited. In vitro studies as well as studies in animals and humans indicate that hyperhomocysteinemia induces dysfunction of the vascular endothelium, with loss of endothelium-dependent vasodilation and endothelial antithrombotic properties, and proliferation of vascular smooth muscle cells, which are key processes in current models of atherogenesis and thrombosis. One of the hypotheses is that homocysteine can lead to cellular dysfunction through a mechanism involving oxidative damage but future studies in humans are needed to confirm this. Studies in hyperhomocysteinemic vascular patients have shown that endothelial antithrombotic properties appear to be more severely impaired than in similar patients with normohomocysteinemia. Furthermore, impaired endothelium-dependent vasodilation has been observed in clinically healthy hyperhomocysteinemic subjects in whom no abnormalities were found in endothelial antithrombotic properties. Future studies involving homocysteine-lowering treatment in hyperhomocysteinemic patients with vascular disease and in clinically healthy hyperhomocysteinemic subjects are necessary to investigate the mechanisms by which homocysteine causes atherothrombotic disorders in humans.
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PMID:Hyperhomocysteinemia and atherothrombotic disease. 976 55

Despite intense investigation, mechanisms linking the development of occlusive vascular disease with elevated levels of homocysteine (HCY) are still unclear. The vascular endothelium plays a key role in regulating thrombogenesis and thrombolysis. We hypothesized that vascular lesions in individuals with elevated plasma HCY may be related to a dysfunction of the endothelium triggered by HCY. We investigated the effect of HCY on human neutrophil adhesion to and migration through endothelial monolayers. We also examined the effect of HCY on leukocyte adhesion and migration in mesenteric venules of anesthetized rats. We found that pathophysiological concentrations of HCY in vitro induce increased adhesion between neutrophils and endothelial cells. This contact results in neutrophil migration across the endothelial layer, with concurrent damage and detachment of endothelial cells. In vivo, HCY infused in anesthetized rats caused parallel effects, increasing leukocyte adhesion to and extravasation from mesenteric venules. Our results suggest that extracellular H2O2, generated by adherent neutrophils and/or endothelial cells, is involved in the in vitro endothelial cell damage. The possibility exists that leukocyte-mediated changes in endothelial integrity and function may lead to the vascular disease seen in individuals with elevated plasma HCY.
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PMID:Homocysteine enhances neutrophil-endothelial interactions in both cultured human cells and rats In vivo. 1006 75

Advanced glycation end products (AGEs) have been implicated as causal factors in the vascular complications of diabetes and it is known that these products interact with cells through specific receptors. The AGE-receptor complex, originally described as p60 and p90, has been characterised in hemopoietic cells and the component proteins identified and designated AGE-R1, -R2 and -R3. In the current study we have characterised this receptor in human umbilical vein endothelial cells (HUVECs) and elucidated several important biological properties which may impact on AGE mediated vascular disease. 125I-AGE-BSA binding to HUVEC monolayers was determined with and without various cold competitors. The synthetic AGE, 2-(2-furoyl)-4(5)-furanyl-1H-imidazole (FFI)-BSA, failed to compete with AGE-BSA binding unlike observations already reported in hemopoietic cells. The ability of 125I-AGE-BSA to bind to separated HUVEC plasma membrane (PM) proteins was also examined and the binding at specific bands inhibited by antibodies to each component of the AGE-receptor complex. Western blotting of whole cell and PM fractions, before and after exposure to AGE-BSA, revealed that AGE-R1, -R2 and -R3 are subject to upregulation upon exposure to their ligand, a phenomenon which was also demonstrated by immunofluorescence of non-permeabilised cells. mRNA expression of each AGE-receptor component was apparent in HUVECs, with the AGE-R2 and -R3 gene expression being upregulated upon exposure to AGEs in a time-dependent manner. A phosporylation assay in combination with AGE-R2 immunoprecipitation demonstrated that this component of the receptor complex is phosphorylated by acute exposure to AGE-BSA. These results indicate the presence of a conserved AGE-receptor complex in vascular endothelium which demonstrates subtle differences to other cell-types. In response to AGE-modified molecules, this complex is subject to upregulation, while the AGE-R2 component also displays increased phosphorylation possibly leading to enhanced signal transduction.
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PMID:Characterization of the advanced glycation end-product receptor complex in human vascular endothelial cells. 1008 Sep 35

1. In the normal blood vessel, the vascular endothelium regulates the tone of the underlying smooth muscle and the reactivity of blood elements, such as platelets and neutrophils, by the release of mediators, in particular nitric oxide (NO) and endothelin-1 (ET-1). 2. Nitric oxide is a potent vasodilator that also inhibits platelet and neutrophil aggregation and adhesion; ET-1 is the most potent mammalian vasoconstrictor peptide yet found. Recently, much research effort has focused on examining the interactions between these two important mediators. At a simple level, ET-1 acts on specific receptors on the endothelium to increase the release of NO, while NO depresses the production and/or release of ET-1 from endothelial cells. 3. While ET-1 appears to have a relatively small influence on the basal regulation of blood pressure, NO appears central. For example, inhibition of NO production in normotensive animals produces a marked elevation in blood pressure. 4. Conversely, numerous vascular disease states have been associated with elevations in the production and/or release of ET-1 and it has been implicated in the deleterious changes associated with ischaemia-reperfusion injury, subarachnoid haemorrhage and hypertension. In these conditions, NO production may also be increased by the induction of NO synthetic pathways within the vascular smooth muscle. Endothelin-1 may also be produced by the vascular smooth muscle under similar circumstances. 5. Therefore, in pathological states, a new balance between NO and ET-1 production may be central to changes in blood vessel reactivity, smooth muscle proliferation and blood coagulability.
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PMID:Relationships between the endothelin and nitric oxide pathways. 1008 22

Graft vascular disease after solid organ transplantation is a main complication that limits long-term survival of the graft. An injury of the endothelium and subsequent vascular response is considered to be responsible for smooth muscle cell hyperplasia with resulting luminal narrowing. What is less certain are the precise steps leading to endothelial injury and subsequent vessel disease. Since the immunosuppressive drug azathioprine is in clinical use due to its antiproliferative effect on lymphocytes, we were interested in how far it exerts effects on the vascular endothelium. Azathioprine and its metabolite 6-mercaptopurine, a potent inhibitor of purine salvage pathway enzymes, dose dependently led to decreased endothelial cell proliferation as well as to decreases in intracellular purine nucleotides adenosine-triphosphate and guanosine-triphosphate. By increasing the formation of the pyrimidine nucleotide uridine-triphosphate within 24 hours, azathioprine and its metabolite altered the endothelial nucleotide balance. Since not only the formation of toxic thio- and methylthiopurines (thio-guanosine-monophosphate, methyl-thio-inosine-monophosphate) was measured, the activity of the enzyme thiopurinemethyltransferase was induced (3.21+/-2.04 U per 10(9) cells, mean+/-SD). These findings indicate that the vascular endothelium plays an active role in the metabolization of the established immunosuppressant azathioprine that then exerts specific toxic effects on endothelial cells.
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PMID:Azathioprine and 6-mercaptopurine alter the nucleotide balance in endothelial cells. 1023 Aug 93

Elevated plasma homocysteine levels are associated with vascular disease and thrombosis. Premature atherosclerosis and thromboembolism are seen in children who are homozygotes for defects in enzymes responsible for the metabolism of homocysteine. Adults with heterozygous defects have less marked elevations of homocysteine, and onset of atherosclerosis and vascular disease are delayed into the fourth and fifth decade of life. Homocysteine can damage vascular endothelium, cause proliferation of vascular smooth muscle, activate platelets, promote lipid peroxidation, and activate the coagulation cascade. Epidemiologic studies have linked elevations in plasma homocysteine with coronary artery disease, cerebrovascular disease, and thromboembolism. Folic acid, in combination with vitamins B6 and B12, can normalize homocysteine levels in most patients. Although randomized trials assessing the efficacy of homocysteine reduction have yet to be completed, treatment with vitamin supplementation should be considered in all patients at risk for vascular disease.
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PMID:Homocysteine: evidence for a causal relationship with cardiovascular disease. 1034 72

Cell adhesion molecules are substances with a protein character expressed on the cell surface of all tissues. They participate in the control of basic vital processes, in processes of embryogenesis, cellular growth and differentiation, they ensure the interaction of cells with the environment. At present four main classes of cytoadhesion molecules are known: integrins, the immunoglobulin group of adhesion molecules, cadherins and selectins. Cytoadhesion molecules play an important role in the pathophysiology of cardiovascular, neoplastic, infectious and skin diseases. Some cardiovascular diseases are associated with pathological impairment of the structure and function of endothelial cells-with endothelial dysfunction. In case of damage or inflammatory processes of the blood vessels due to the action of released cytokines increased expression of adhesion molecules of the integrin, selectin and immunoglobulin groups occurs and subsequently increased adhesion and migration of inflammatory cells across the vascular wall. Impaired function of the vascular endothelium is also the first step in the genesis and development of chronic vascular disease--atherosclerosis. In the initial stage of development of atherosclerosis--during rolling, adhesion and migration of leucocytes across the endothelium the cytoadhesion molecules play a crucial role.
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PMID:[Cell adhesion molecules and their role in pathophysiologic processes]. 1042 26

ENDOGLIN codes for a homodimeric membrane glycoprotein that interacts with receptors for members of the TGF-beta superfamily and is the gene mutated in the autosomal dominant vascular disorder hereditary hemorrhagic telangiectasia type 1 (HHT1). We recently demonstrated that functional endoglin was expressed at half levels on human umbilical vein endothelial cells (HUVECs) and peripheral blood activated monocytes from HHT1 patients. Two types of mutant protein were previously analyzed, the product of an exon 3 skip which was expressed as a transient intracellular species and prematurely truncated proteins that were undetectable in patient samples. Here we report the analysis of four proteins resulting from point mutations, with missense codons G52V and C53R in exon 2, W149C in exon 4 and L221P in exon 5. Metabolic labeling of activated monocytes from confirmed, clinically affected patients revealed reduced expression of fully processed normal endoglin in all cases. Pulse-chase analysis with HUVECs from a newborn with the C53R substitution indicated that mutant endoglin remained intracellular as a precursor form and did not impair processing of the normal protein. Biotinylation of cell surface proteins, metabolic labeling and pulse-chase analysis revealed that none of the engineered missense mutants was significantly expressed at the surface of COS-1 transfectants. Thus, these four HHT1 missense mutations lead to transient intracellular species which cannot interfere with normal endoglin function. These data suggest that haploinsufficiency, leading to reduced levels of one of the major surface glyco-proteins of vascular endothelium, is the predominant mechanism underlying the HHT1 phenotype.
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PMID:Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1. 1054 96

Central retinal vein occlusion (CRVO) is usually seen in older adults and is often associated with systemic vascular disease, this is much less evident in young people. A case report of a 28-year-old woman presented a central retinal vein occlusion in her left eye. This young woman was treated with antiandrogenic drug. Investigations revealed an abnormality of the hemostatic system. The central retinal vein occlusion was resolved and the fundus assumed a normal appearance one-month after the primary episode. Retinal vascular occlusions with antiandrogenic drug may be due to three mechanisms: increased platelet cell aggregation, alteration of fibrinolytic system and vascular endothelium hyperplasia.
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PMID:[Central retinal vein occlusion in a patient treated with antiandrogenic drug]. 1066 Jun 47


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