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 genome of Chlamydophila caviae (formerly Chlamydia psittaci, GPIC isolate) (1 173 390 nt with a plasmid of 7966 nt) was determined, representing the fourth species with a complete genome sequence from the Chlamydiaceae family of obligate intracellular bacterial pathogens. Of 1009 annotated genes, 798 were conserved in all three other completed Chlamydiaceae genomes. The C.caviae genome contains 68 genes that lack orthologs in any other completed chlamydial genomes, including tryptophan and thiamine biosynthesis determinants and a ribose-phosphate pyrophosphokinase, the product of the prsA gene. Notable amongst these was a novel member of the virulence-associated invasin/intimin family (IIF) of Gram-negative bacteria. Intriguingly, two authentic frameshift mutations in the ORF indicate that this gene is not functional. Many of the unique genes are found in the replication termination region (RTR or plasticity zone), an area of frequent symmetrical inversion events around the replication terminus shown to be a hotspot for genome variation in previous genome sequencing studies. In C.caviae, the RTR includes several loci of particular interest including a large toxin gene and evidence of ancestral insertion(s) of a bacteriophage. This toxin gene, not present in Chlamydia pneumoniae, is a member of the YopT effector family of type III-secreted cysteine proteases. One gene cluster (guaBA-add) in the RTR is much more similar to orthologs in Chlamydia muridarum than those in the phylogenetically closest species C.pneumoniae, suggesting the possibility of horizontal transfer of genes between the rodent-associated Chlamydiae. With most genes observed in the other chlamydial genomes represented, C.caviae provides a good model for the Chlamydiaceae and a point of comparison against the human atherosclerosis-associated C.pneumoniae. This crucial addition to the set of completed Chlamydiaceae genome sequences is enabling dissection of the roles played by niche-specific genes in these important bacterial pathogens.
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PMID:Genome sequence of Chlamydophila caviae (Chlamydia psittaci GPIC): examining the role of niche-specific genes in the evolution of the Chlamydiaceae. 1268 64

Infection with Chlamydia pneumoniae has been implicated as a potential risk factor for atherosclerosis. This study was designed to investigate the mechanisms of the anti-chlamydial activity of aspirin. A reporter gene assay for NF-kappa B activity, immunoblot analysis for cyclo-oxygenase (COX)-2 and radioimmunoassay for prostaglandin E(2) (PGE(2)) were performed. Following infection of HEp-2 cells with C. pneumoniae, NF-kappa B was activated, COX-2 was induced and PGE(2) was elevated. Aspirin inhibited NF-kappa B activation at a concentration of 0.1 mM, partially inhibited COX-2 induction and blocked PGE(2) synthesis completely. In addition, high doses of aspirin (1 and 2 mM) inhibited chlamydial growth in HEp-2 cells, decreasing the number and size of inclusion bodies; this effect could be overcome by adding tryptophan to the culture. Indomethacin also blocked the synthesis of PGE(2), but had no effect on COX-2 expression or chlamydial growth. These results indicate that aspirin not only has an anti-inflammatory activity through prevention of NF-kappa B activation but also has anti-chlamydial activity at high doses, possibly through depletion of tryptophan in HEp-2 cells.
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PMID:Aspirin inhibits Chlamydia pneumoniae-induced NF-kappa B activation, cyclo-oxygenase-2 expression and prostaglandin E2 synthesis and attenuates chlamydial growth. 1272 17

Several studies have demonstrated that the isoflavone genistein exerts a protective effect against lipid peroxidation of low density lipoproteins (LDL). Aim of our study was to investigate whether genistein protects high density lipoproteins (HDL), isolated from normolipemic subjects, against Cu(++)-induced lipid peroxidation. Our results demonstrated that genistein exerts an inhibitory effect against Cu(++)-induced lipid peroxidation of HDL, as shown by the lower increase in the levels of conjugated dienes in lipoproteins oxidized after preincubation with different concentrations of genistein (0.5-2.5microM). Moreover the analysis of fluorescence emission spectra of tryptophan (Trp) and Laurdan (6-dodecanoyl-2-dimethyl-aminonaphthalene) demonstrated that genistein prevents the alterations of apoprotein structure and physico-chemical properties, associated with Cu(++)-triggered lipid peroxidation of lipoproteins. The protective effect exerted by genistein against oxidative damage of lipoproteins was realized at concentrations similar to those observed in plasma of human subjects consuming a traditional soy diet or receiving a soy supplement. Therefore, we suggested that antioxidant activity exerted by genistein against lipid peroxidation of HDL in vitro could be of physiological relevance.
Atherosclerosis 2004 Jan
PMID:Effect of genistein against copper-induced lipid peroxidation of human high density lipoproteins (HDL). 1470 57

Tibetan herbal remedy PADMA 28 revealed promising results to support treatment of intermittent claudication, atherosclerosis and chronic hepatitis. The remedy was confirmed to be closely linked with anti- and pro-oxidative properties in vitro. In this study, effect of PADMA 28 was investigated in stimulated and unstimulated human peripheral blood mononuclear cells (PBMC) in vitro. Neopterin production and tryptophan degradation were measured in supernatants of PBMC in the presence or absence of mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A). Stimulation of PBMC induced neopterin formation and tryptophan degradation (p<0.001 compared to unstimulated PBMC), and PADMA 28 inhibited both immunobiochemical effects (p<0.001) in a concentration-dependent manner. Higher concentrations of PADMA 28 were more effective and were able to completely block the pathways induced upon mitogenic stimulation. Data allow to conclude that PADMA 28 is able to inhibit immunobiological effects in stimulated PBMC in vitro. The suppression of neopterin production and tryptophan degradation suggests a specific influence on biochemical pathways induced by Th1-type cytokine interferon-gamma.
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PMID:PADMA 28 modulates interferon-gamma-induced tryptophan degradation and neopterin production in human PBMC in vitro. 1513 23

Oxidative modification of low density lipoprotein (LDL) is involved in the pathogenesis of atherosclerosis and coronary heart disease, which are low in the Mediterranean area possibly due to a high dietary proportion of plant foods. Ethanolic extracts were prepared from more than 120 Mediterranean edible plants collected in remote areas (which maintain their traditional diet) and their antioxidant potential was studied. Extracts derived from Agaricus campestris, Cynara cardunculus, Thymus pulegioides, and Vicia faba were subjected to further analysis in this study. The extracts' potential to scavenge the DPPH radical (2,2-diphenyl-1-picrylhydrazyl radical) and hypochlorous acid (HOCl), as well as their antioxidant capacity, was comparable to the those obtained for standard antioxidants (e.g., quercetin, Trolox). Myeloperoxidase (MPO) catalyzes the production of the highly chlorinating and oxidizing agent HOCl, which reacts with the LDL apoprotein moiety, leading to the derivatization of its aminoacidic residues. Coincubation with extracts significantly prevented HOCl-induced modification of the LDL residue tryptophan, whereas higher concentrations were required to retard lysine damage. Moreover, the extracts inhibited MPO-catalyzed guaiacol oxidation in a concentration-dependent manner in a cell-free assay but, in contrast, did not affect MPO activity in isolated human neutrophils. MPO is also known to facilitate nitric dioxide oxidation. The formation of 3-nitrotyrosine was significantly lower in bovine endothelial aortic cells incubated with C. cardunculus or T. pulegioides. In synthesis, our study shows that local Mediterranean plant foods prevent HOCl toxicity in vitro and, thus, suggests further mechanisms responsible for the reported health-beneficial effect of the Mediterranean diet.
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PMID:Hypochlorous acid scavenging properties of local Mediterranean plant foods. 1573 21

Since alterations of tryptophan metabolism have been reported in diabetes and atherosclerosis, it was thought of interest to investigate any role of cloricromene through the influence on the oxidative metabolism of the amino acid by using diabetic/hyperlipidemic rabbits. Male 4-month-old New Zealand white rabbits, fed a diet enriched with 1% cholesterol and 10% corn oil, were made diabetic with alloxan. During the hyperlipidemic diet, a group of rabbits was treated with cloricromene (10 mg/kg/day subcutaneously plus 1.5 mg/kg/day intravenously, for 5 weeks). The other group received saline. Normometabolic New Zealand rabbits fed standard diet, treated or not with cloricromene, were used as control. The specific activities of liver tryptophan 2,3-dioxygenase and small intestine indole 2,3-dioxygenase were not significantly changed by the drug treatment. Also the specific activities of other enzymes of the kynurenine pathway in the liver and kidneys, specifically kynurenine 3-monooxygenase, kynureninase and kynurenine-oxoglutarate transaminase, did not show any significant difference in both tissues between the two groups of rabbits. On the contrary, 3-hydroxyanthranilate 3,4-dioxygenase activity in the liver of diabetic/hyperlipidemic rabbits and control rabbits treated with cloricromene showed a slight increase in comparison with untreated animals. Conversely, the specific activity of the enzyme in kidneys was not affected by the drug treatment in diabetic/hyperlipidemic animals but was reduced in controls. Aminocarboxymuconate-semialdehyde decarboxylase specific activity remained unchanged in the liver following cloricromene treatment, instead the specific activity of the enzyme in the kidneys of the diabetic/hyperlipidemic rabbits was significantly increased by the drug, with a value more than double in comparison to untreated animals. The activity of the scavenger enzyme Cu/Zn superoxide dismutase (Cu/Zn SOD) in the small intestine was also determined and found significantly increased of about twice as much in the group of diabetic/hyperlipidemic rabbits treated with cloricromene. In conclusion, in diabetic/hyperlipidemic rabbits, cloricromene appeared to influence the enzymes involved in the last steps of tryptophan oxidative metabolism through the kynurenine pathway. This, together with the antioxidant action through the activation of Cu/Zn SOD, might deserve further investigation for evaluating any link between the observed experimental findings at the level of the kynurenine pathway and the clinical effect of the drug.
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PMID:Cloricromene effect on the enzyme activities of the tryptophan-nicotinic acid pathway in diabetic/hyperlipidemic rabbits. 1612 32

Plant proteins have a reduced content of essential amino acids in comparison to animal proteins. A significant reduction of limiting amino acids (methionine, lysine, tryptophan) means lower protein synthesis. In subjects with predominant or exclusive consumption of plant food a higher incidence of hypoproteinemia due to significant reduction of methionine and lysine intakes was observed. On the other hand, lower intake of these amino acids provides a preventive effect against cardiovascular disease via cholesterol regulation by an inhibited hepatic phospholipid metabolism. Vegetarians have a significantly higher intake of non-essential amino acids arginine and pyruvigenic amino acids glycine, alanine, serine. When plant protein is high in non-essential amino acids, down-regulation of insulin and up-regulation of glucagon is a logical consequence. The action of glucagon in the liver is mediated by stimulation of adenyl cyclase that raises cyclic-AMP (adenosine-3,5-monophosphate) concentrations. Cyclic-AMP down-regulates the synthesis of a number of enzymes required for de novo lipogenesis and cholesterol synthesis, up-regulates key gluconeogenic enzymes and the LDL receptors and decreases the IGF-1 activity (insulin-like growth factor). Cyclic-AMP thus provides a reduction of atherosclerosis risk factors as well as a retardation of cancer development. A sufficient consumption of plant proteins has the protective effects against chronic degenerative diseases (Tab. 2, Ref. 26).
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PMID:Health benefits and risks of plant proteins. 1620 43

Heme oxygenase (HO)-1 is important in the vascular system, and its genetic or pharmacological induction in endothelium would be effective for the prevention and treatment of atherosclerosis. The naturally occurring antioxidant 3-hydroxyanthranilic acid (HA), one of l-tryptophan metabolites formed in vivo along the metabolic route known as the kynurenine pathway during inflammation or infection, was found to induce HO-1 expression and to stimulate nuclear translocation of NF-E2 related factor 2 (Nrf2) in human umbilical vein endothelial cells (HUVECs). Pre-treatment with HA inhibited the secretion of monocyte chemoattractant protein (MCP)-1, the expression of vascular cell adhesion molecule (VCAM)-1 and the activation of transcriptional nuclear factor (NF)-kappaB in HUVECs stimulated with tumor necrosis factor-alpha, the major pro-inflammatory cytokine causing endothelial inflammation. Interestingly, the observed anti-inflammatory effects of HA were mimicked by a HO-1 inducer, cobalt protoporphyrin, and bilirubin, one of HO-1 enzymatic products, but abolished in the presence of a HO-1 inhibitor, tin protoporphyrin. Based on our findings, we suggest that Nrf2-dependent HO-1 expression induced by HA inhibits MCP-1 secretion, VCAM-1 expression and NF-kappaB activation associated with vascular injury and inflammation in atherosclerosis.
Atherosclerosis 2006 Aug
PMID:3-Hydroxyanthranilic acid, one of L-tryptophan metabolites, inhibits monocyte chemoattractant protein-1 secretion and vascular cell adhesion molecule-1 expression via heme oxygenase-1 induction in human umbilical vein endothelial cells. 1624 46

Because alpha-tocopherol (alpha-TOH) mediates the peroxidation of cholesterol-esterified lipids in human low-density lipoprotein (LDL) in vitro and has displayed disappointing results against the onset and development of atherosclerosis, it may not be appropriate for use as a therapeutic in the prevention and/or treatment of the disease. Herein are described the experimental results demonstrating that 3-pyridinols spare alpha-TOH, do not efficiently mediate lipid peroxidation, and protect lipoprotein tryptophan residues in human LDL.
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PMID:Lipid-soluble 3-pyridinol antioxidants spare alpha-tocopherol and do not efficiently mediate peroxidation of cholesterol esters in human low-density lipoprotein. 1625 Jun 37

We investigated the extent to which tobacco smoke could induce persistence of Chlamydia pneumoniae in human endothelial cells. Aortic and coronary artery endothelia were infected in the absence or presence of non-cytotoxic concentrations of tobacco smoke medium. Following exposure to smoke medium, chlamydial inclusions were smaller and demonstrated fewer genome copies as determined by real-time PCR. Enumeration of inclusion-forming units (IFU) established a significant smoke-mediated, dose-dependent inhibition of elementary bodies (EB). Host cell apoptosis did not contribute to the observed restriction of productive infection. Ultrastructure analysis demonstrated an arrest in chlamydial development following smoke-exposure, with a predominance of reticulate bodies (RB) observed inside inclusions. Recovery of viable IFU was achieved with removal of smoke-medium and addition of L-tryptophan. In the presence of smoke, C. pneumoniae infection demonstrated all the characteristics of persistence in human endothelia cells. This is the first time that primary human arterial endothelial cells have been shown to support chlamydial persistence. Tobacco smoke is a well-characterized risk factor for progression of atherosclerosis, but a novel means of inducing chlamydial persistence in vascular cells. Thus, smoking may additionally contribute to atherosclerotic disease by inducing a persistent chlamydial infection in arterial endothelium.
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PMID:Tobacco smoke induces a persistent, but recoverable state in Chlamydia pneumoniae infection of human endothelial cells. 1627 47


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