Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The participation of leukocytes in the development of vascular disorders has been observed under various circumstances. Leukocyte activation occurs in extracorporeal blood circulation which lead to a pulmonary vascular sequestration and respiratory distress syndrome. Leukocytes could act on vascular components through at least two different pathways by releasing free oxygen radicals and proteases or by producing mediators such as interleukin 1, Tumor necrosis alpha, leukotrienes. Monocytes macrophages are present in the vascular wall at a very early stage of atherosclerosis. A majority of foam cells have been identified as macrophages loaded with lipids. Lymphocytes and monocytes are present in the atherosclerotic plaque. Leukocytes are also observed in the inflammatory lesion of vasculitis and experimentally activated lymphocytes can induce vasculitis. The molecular bases of leukocyte-endothelium interactions have been determined, and imply specialized molecules. Leukocyte Adhesion Molecule (LeucAM) appear to play a crucial role in leukocyte adhesion. On the endothelial cell side, endothelial cell adhesion molecule, intercellular adhesion molecule are receptors for leukocytes adhesion. They have been recently fully characterized. The better knowledge of leukocyte-vascular wall interactions offers new possible target for therapeutic agents.
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PMID:[Leukocytes and vascular lesions]. 204 28

Fibrinolytic system, immune reactivity and isoelectric focusing of serum albumin were examined in 94 patients exhibiting combination of obstructive lung disease (chronic obstructive bronchitis and bronchial asthma) with atherosclerosis. Plasminogen activator showed discrete activity, the discreteness being less in respiratory distress of the I degree but higher in the distress of the II and III degree. Relative number of E-RFC and monocytes expressing receptors to IgM and IgG Fc-fragment decreased. Percentage of EAC-RFC rose. Serum albumin fractions changed pH range due to modification of albumin molecules resultant from forming complexes with fibrinogen degradation products. Concentration of the latter under conditions of respiratory distress induced by obstructive lung diseases associated with atherosclerosis substantially exceeded the standard levels.
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PMID:[Fibrinolysis, immune reactivity and the structure of the blood serum albumin in obstructive lung diseases combined with atherosclerosis]. 207 78

In recent years it has become apparent that peroxynitrite, which is one of the toxic metabolites originating from the reaction of nitric oxide and superoxide presents a number of pathologic states in which free radicals are thought to be involved. Peroxynitrite is capable of oxidizing a wide variety of biomolecules including plasma, proteins, lipids, carbohydrates and nucleic acids. Peroxynitrite is involved in the hydroxylation of aromatic compounds and acts as a nitrating agent. It modifies free or protein-associated tyrosine residues to give nitrotyrosines, leaving a marker detectable in vivo. Peroxynitrite has been implicated in the pathophysiology of a variety of diseases including inflammation, atherosclerosis, arthritis, endotoxemia, ischaemia-reperfusion injury, or acute respiratory distress syndrome. Development of specific peroxynitrite scavengers may provide new approaches for the effective treatment of these disease states.
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PMID:Peroxynitrite: a putative cytotoxin. 955 87

Neutrophils and other phagocytes manufacture O(2)(-) (superoxide) by the one-electron reduction of oxygen at the expense of NADPH. Most of the O(2)(-) reacts with itself to form H(2)O(2) (hydrogen peroxide). From these agents a large number of highly reactive microbicidal oxidants are formed, including HOCl (hypochlorous acid), which is produced by the myeloperoxidase-catalyzed oxidation of Cl(-) by H(2)O(2); OH(*) (hydroxyl radical), produced by the reduction of H(2)O(2) by Fe(++) or Cu(+); ONOO(-) (peroxynitrite), formed by the reaction between O(2)(-) and NO(*); and many others. These reactive oxidants are manufactured for the purpose of killing invading microorganisms, but they also inflict damage on nearby tissues, and are thought to be of pathogenic significance in a large number of diseases. Included among these are emphysema, acute respiratory distress syndrome, atherosclerosis, reperfusion injury, malignancy and rheumatoid arthritis.
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PMID:Phagocytes and oxidative stress. 1093 76

Endothelin-1 (ET-1) is increasingly recognized as a proinflammatory mediator in various diseases, such as atherosclerosis and acute respiratory distress syndrome (ARDS). Angiopoietin-1 (Ang-1), a ligand of the endothelial receptor Tie2, inhibits endothelial apoptosis, reduces vascular leakage, and suppresses the induction of inflammatory markers, indicating that it has diverse vasoprotective, anti-inflammatory actions. Thus, we examined the effects of Ang-1 on ET-1 production in vitro and in vivo and investigated cell-based gene transfer of Ang-1 in a rat model of lipopolysaccharide (LPS)-induced ARDS. Cultured human endothelial cells were treated with recombinant Ang-1 with or without tumor necrosis factor-alpha (TNF-alpha) (100 U/ml). ET-1 release into the culture medium after 24 hrs was determined by enzyme-linked immunosorbent assay. Levels of preproendothelin-1 (ppET-1) mRNA were measured by quantitative reverse transcription-polymerase chain reaction. Fisher344 rats were subjected to cell-based gene transfer to the lung circulation by injecting syngeneic fibroblasts transfected with Ang-1 cDNA or a null plasmid vector. After 24 hrs, LPS (100 microg/kg body wt) was instilled intratracheally to induce pulmonary inflammation. Bronchoalveolar lavage was performed 6 hrs later, and lungs were harvested for histologic and molecular analyses. ET-1 release from cultured endothelial cells was dose-dependently reduced by Ang-1, which also prevented induction of ET-1 release by TNF-alpha (P < 0.05). RNA expression of ppET-1 was similarly reduced. In LPS-challenged lungs, ppET-1 RNA was induced 3.4-fold, and ET-1 protein in lavage fluid was increased 5.6-fold (P < 0.05). Ang-1 gene transfer attenuated the LPS-induced increases in ppET-1 RNA and lavage ET-1 protein by 34% and 33%, respectively (P < 0.05). The downregulation of ET-1 correlated with the amelioration of pulmonary inflammation, as indicated by reductions in leukocyte infiltration (by 43%) and intra-alveolar septal thickening (by 40%). These results show that ET-1 transcript and protein levels are downregulated by Ang-1 in both in vitro and in vivo systems and that cell-based Ang-1 gene transfer markedly ameliorated inflammation in vivo in an experimental model of ARDS. Thus, cell-based gene transfer of Ang-1 may provide a novel treatment strategy for ARDS by attenuating vascular inflammation via suppression of ET-1.
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PMID:Regulation of endothelin-1 by angiopoietin-1: implications for inflammation. 1674 Oct 35

Head and neck irradiation may lead to accelerated atherosclerosis over several years. Delayed stroke has been described after head and neck irradiation administered for a number of conditions. However, brain stem stroke has only rarely been associated with irradiation. We report a patient with medullary hemorrhagic infarction 6 years after radiotherapy for nasopharyngeal carcinoma. A 42-year-old normotensive Chinese male had rapid onset of vertigo, diplopia, ataxia, dysphagia, hypophonic dysarthria, hemiparesis, and respiratory distress. Cranial MR imaging 2 days after symptom onset showed medullary infarction, and cranial MR imaging 5 days after symptom onset showed medullary hemorrhage. He needed ventilatory support and died of bacterial pneumonia 1 month later. Other risk factors for stroke were absent. Hemorrhagic infarction in this patient was likely associated with the radiotherapy. Radiotherapy is the first choice of treatment for nasopharyngeal carcinoma, however, it may induce fatal medullary hemorrhagic infarction.
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PMID:Medullary hemorrhagic infarction after radiation for nasopharyngeal carcinoma. 1747

Oxidative stress has been widely recognized to be involved in the pathogenesis of cardiopulmonary disorders. In ischemic heart diseases, it is involved not only in the development of atherosclerosis but also in ongoing ischemic injury, especially in the reperfusion process. Cardiomyopathy is another cardiac disorder in which oxidative stress is involved. In diabetic cardiomyopathy, homocysteine, a well-known source of oxidative stress, is believed to play major roles in its development. Thioredoxin (TRX) is a redox-acting protein ubiquitously present in the human body. It also is inducible by a wide variety of oxidative stresses. TRX is a multifunctional protein and has anti-inflammatory and antiapoptotic effects, as well as antioxidative effects. It is therefore feasible to think that TRX is a potential therapy for cardiac disease. Moreover, serum TRX is a well-recognized biomarker of various diseases involving oxidative stress, and this is also the case for cardiac disorders. Here we discuss how TRX is useful as a biomarker of and therapeutic agent for cardiopulmonary disorders, especially focusing on ischemic heart disease, myocarditis and oxygen sensing, and acute respiratory distress syndrome.
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PMID:From oxygen sensing to heart failure: role of thioredoxin. 1751 84

Reactive oxygen species (ROS) including superoxide (O(2)(.-)) and hydrogen peroxide (H(2)O(2)) are produced endogenously in response to cytokines, growth factors; G-protein coupled receptors, and shear stress in endothelial cells (ECs). ROS function as signaling molecules to mediate various biological responses such as gene expression, cell proliferation, migration, angiogenesis, apoptosis, and senescence in ECs. Signal transduction activated by ROS, "oxidant signaling," has received intense investigation. Excess amount of ROS contribute to various pathophysiologies, including endothelial dysfunction, atherosclerosis, hypertension, diabetes, and acute respiratory distress syndrome (ARDS). The major source of ROS in EC is a NADPH oxidase. The prototype phagaocytic NADPH oxidase is composed of membrane-bound gp91phox and p22hox, as well as cytosolic subunits such as p47(phox), p67(phox) and small GTPase Rac. In ECs, in addition to all the components of phagocytic NADPH oxidases, homologues of gp91(phox) (Nox2) including Nox1, Nox4, and Nox5 are expressed. The aim of this review is to provide an overview of the emerging area of ROS derived from NADPH oxidase and oxidant signaling in ECs linked to physiological and pathophysiological functions. Understanding these mechanisms may provide insight into the NADPH oxidase and oxidant signaling components as potential therapeutic targets.
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PMID:NADPH oxidase-dependent signaling in endothelial cells: role in physiology and pathophysiology. 1878 13

The levels of circulating oxidized phospholipids (OxPLs) become increased in chronic and acute pathologic conditions such as hyperlipidemia, atherosclerosis, increased intimamedia thickness in the patients with systemic Lupus erythematosus, vascular balloon injury, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). These pathologies are associated with inflammation and activation of endothelial cells. Depending on the biological context and the specific group of phospholipid oxidation products, OxPL may exhibit both proinflammatory and anti-inflammatory effects. This review will summarize the data showing a dual role of OxPL in modulation of chronic and acute inflammation as well as OxPL effects on pulmonary endothelial permeability. Recent reports show protective effects of OxPL in the models of endotoxin and ventilator-induced ALI and suggest a potential for using OxPL-derived cyclopenthenone-containing compounds with barrier-protective properties for drug design. These compounds may represent a new group of therapeutic agents for the treatment of lung syndromes associated with acute inflammation and lung vascular leak.
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PMID:Oxidized phospholipids in control of inflammation and endothelial barrier. 1930 75

Variants in the 5-lipoxygenase (ALOX5) gene are first-line candidate causes for interindividual differences in diseases where leukotrienes play a key role, e.g., inflammatory and immune diseases, atherosclerosis, asthma or the acute respiratory distress syndrome (ARDS). We developed and validated Pyrosequencing screening assays for single nucleotide polymorphism (dbSNP-IDs rs4986832, rs4987105, rs2115819, rs3740107, rs1565096, rs2291427, rs10571382, rs2242334, rs2229136, rs3802548), and a capillary electrophoresis assay for the ALOX5 Sp1/Egr1 promoter tandem repeat polymorphism. This selection spans the whole ALOX5 gene range and includes all variants with reported functional associations. A gene structure analysis in DNAs from 187 healthy unrelated Caucasians revealed two haploblocks, one in the promoter and one spanning six SNPs from rs3740107G>A in intron 6 to rs2229136A>G in exon 13. The five-repeat genotype was the most frequent Sp1/Egr1 promoter tandem repeat variant (allelic frequency 84%). These assays and analyses provide a solid basis for future assessments of the genetic modulation of leukotriene production.
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PMID:Functional variants of the human 5-lipoxygenase gene and their genetic diagnosis. 1944 47


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