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)

Oxidative stress plays a pivotal role in the pathogenesis of atherosclerosis and can be effectively influenced by radical scavenging enzyme activity and expression. The vasoprotective effects of estrogens may be related to antioxidative properties. Therefore, effects of 17beta-estradiol on production of reactive oxygen species and radical scavenging enzymes were investigated. 17beta-estradiol diminished angiotensin II-induced free radical production in vascular smooth muscle cells (DCF fluorescence laser microscopy). 17beta-estradiol time- and concentration-dependently upregulated manganese (MnSOD) and extracellular superoxide dismutase (ecSOD) expression (Northern and Western blotting) and enzyme activity (photometric assay). Nuclear run-on assays demonstrated that 17beta-estradiol increases MnSOD and ecSOD transcription rate. Half-life of MnSOD mRNA was not influenced, whereas ecSOD mRNA was stabilized by estrogen. Copper-zinc SOD, glutathione-peroxidase, and catalase were not affected by estrogen. Estrogen deficiency in ovariectomized mice induced a downregulation of ecSOD and MnSOD expression, which was associated with increased production of vascular free radicals and prevented by estrogen replacement or treatment with PEG-SOD. In humans, increased estrogen levels led to enhanced ecSOD and MnSOD expression in circulating monocytes. Estrogen acts antioxidative at least to some extent via stimulation of MnSOD and ecSOD expression and activity, which may contribute to its vasoprotective effects.
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PMID:Modulation of antioxidant enzyme expression and function by estrogen. 1281 84

Increased concentration of low density lipoprotein (LDL) cholesterol or decreased level of high density lipoprotein (HDL) cholesterol are important risk factors for coronary atherosclerosis. However, an independent association of triglycerides (TG) with atherosclerosis is uncertain. The aim of this prospective study was to evaluate the relationship between serum lipid levels and the extent of coronary atherosclerosis in patients with suspected coronary artery disease (CAD) and no previous myocardial infarction who were not treated with lipids lowering therapy or low-lipid diet. The study was conducted in 141 patients (53.6 +/- 7.8 years old; 32 female) who underwent a routine coronary angiography for CAD diagnosis. A modified angiographic Gensini Score (GS) was used to reflect the extent of coronary atherosclerosis. Fasting serum lipid concentrations were determined using cholesterol esterase/peroxidase (CHOD/PAP) enzymatic method for total cholesterol and its fractions and lipase glycerol kinase (GPO/PAP) enzymatic method TG evaluation. The association of Gensini Score with variables characterising lipid profile was analysed with the use of Pearson correlation (r co-efficient; p value). GS was positively correlated with total cholesterol (r = 0.404; p < 0.001), LDL cholesterol (r = 0.484; p < 0.001 ) and TG (r = 0.235; p = 0.005). There was a negative correlation between Gensini Score and HDL cholesterol (r = -0.396; p < 0.001). In angina pectoris patients with no previous myocardial infarction, the extent of coronary atherosclerosis is positively correlated with pro-atherogenic lipids, i.e. total cholesterol, LDL cholesterol and TG and negatively correlated with antiatherogenic HDL cholesterol.
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PMID:Correlation between the extent of coronary atherosclerosis and lipid profile. 1284 39

Results are submitted of studies designed to measure peroxidase activity in the blood of 41 patient presenting with atherosclerosis-associated cerebrovascular disorders, while receiving microwave resonance therapy. Those patients presenting with cerebrovascular pathology proved to have the peroxidation syndrome as was evidenced by the analysis of the studies made. The above syndrome can be reversed with the aid of the microwave resonance therapy.
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PMID:[Blood peroxidase activity in patients with cerebral atherosclerosis receiving microwave resonance therapy]. 1288 62

The mammalian 1-Cys peroxiredoxin (Prdx6) is a unique member of the peroxiredoxin family of proteins capable of protecting cells from metal-catalyzed oxidative damage. We recently identified Prdx6 as a candidate for the quantitative trait locus Ath1, a gene responsible for a difference in diet-induced atherosclerosis susceptibility in mice. To investigate the role of Prdx6 in atherosclerosis, we generated transgenic mice that overexpress the Prdx6 allele from the Ath1-resistant 129/SvJ strain on an Ath1-susceptible C57BL/6J background. These mice expressed significantly elevated levels of Prdx6 mRNA and protein in multiple tissues including liver, aorta, and peritoneal macrophages, which accumulated significantly lower levels of hydrogen peroxide, revealing an enhanced antioxidant activity in these mice. However, overexpression of Prdx6 had no protective effect on LDL oxidation in vitro, and transgenic mice fed an atherogenic diet for 10 weeks did not possess an increased resistance to atherosclerosis nor did they maintain the high prediet plasma HDL levels consistent with the Ath1-resistant phenotype. In addition, the Prdx6 allele from the susceptible strain was shown to have a higher antioxidant activity than that of the resistant strains. These data suggest that the increased peroxidase activity attributable to Prdx6 overexpression in transgenic mice is not sufficient to protect mice from atherosclerosis, and that Prdx6 is not likely to be the gene underlying Ath1.
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PMID:Overexpression of Prdx6 reduces H2O2 but does not prevent diet-induced atherosclerosis in the aortic root. 1457 13

Insulin-like growth factors (IGFs) play a central role in the integration of proliferative and survival responses of most mammalian cell types. IGF-binding protein-3 (IGFBP-3) influences IGF action directly as a carrier of IGFs but also modulates these actions indirectly via independent mechanisms involving interactions with plasma, extracellular matrix and cell surface molecules, conditional proteolysis, cellular uptake, and nuclear transport. Here we demonstrate that a short C-terminal metal-binding domain (MBD) of IGFBP-3 mediates binding to metals. MBD epitopes, sequestered in the intact molecule, are unmasked by incubation in the presence of ferrous (but not ferric or zinc) ions. An isolated 14-mer MBD peptide triggered apoptotic effects in stressed HEK293 cells as effectively as IGFBP-3. The MBD, which encompasses a nuclear localization sequence and an adjacent putative caveolin-binding sequence, mobilizes rapid cellular uptake and nuclear localization of unrelated proteins such as green fluorescent protein and streptavidin-horseradish peroxidase conjugate. Metal ions stimulate MBD-mediated cellular/nuclear uptake in vivo. Cross-linking studies showed a direct physical interaction of MBD with integrins alphav and beta1, caveolin-1, and transferrin receptor. MBD-mediated protein mobilization and pro-apoptotic effects are inhibited by nystatin but not chlorpromazine, suggesting an involvement of caveolar-mediated endocytosis. However, MBD effects are inhibited by antibodies to transferrin receptor or integrins. These results are discussed with particular reference to the cell target specificity of IGFBP-3 in disease processes such as cancer and atherosclerosis.
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PMID:Insulin-like growth factor-independent effects mediated by a C-terminal metal-binding domain of insulin-like growth factor binding protein-3. 1457 63

It has been reported that oxidized LDL (oxLDL) are involved in the pathogenesis of atherosclerosis, and that macrophages as well as other cells of the arterial wall can oxidize LDL in vitro, depending on the balance between intracellular prooxidant generation and antioxidant defense efficiency. Because of their possible beneficial role in the prevention of atherosclerosis and other oxidative stress-associated diseases, phenolic compounds naturally occurring in vegetables, fruits, and beverages are receiving increased attention. In the present work, we investigated the mechanisms underlying the protective effect exerted by extra virgin olive oil biophenols, namely, protocatechuic acid and oleuropein, on LDL oxidation mediated by murine J774 A.1 macrophage-like cells. The biophenols were added to the cells with LDL and left in the medium during the entire experimental period, or for a period of 2 h and then removed from the medium before the addition of LDL. The effect of biophenols alone was also tested. In both experimental procedures, these antioxidants had the following effects: 1). completely prevented the J774 A.1-mediated oxidation of LDL; 2). counteracted the time-dependent variations in intracellular redox balance, inhibiting the production of O(2)(.-) and H(2)O(2) and the decrease in glutathione (GSH) content; 3). restored glutathione reductase (GR) and peroxidase (GPx) activities; and 4). restored the mRNA expression of gamma-glutamylcisteine synthetase (gammaGCS), GR, and GPx to control values. More importantly, we observed significant overtranscription and increased activities of two antioxidative enzymes, GPx and GR, compared with controls when the biophenols were present in the medium for 2 h and then removed before LDL exposure, or when the cells were exposed to the antioxidants alone for up to 24 h. Our findings suggest that the activation of mRNA transcription of GSH-related enzymes represents an important mechanism in phenolic antioxidative action.
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PMID:Extra virgin olive oil biophenols inhibit cell-mediated oxidation of LDL by increasing the mRNA transcription of glutathione-related enzymes. 1505 26

Paraoxonases PON1 and PON3, which are both associated in serum with HDL, protect the serum lipids from oxidation, probably as a result of their ability to hydrolyze specific oxidized lipids. The activity of HDL-associated PON1 seems to involve an activity (phospholipase A2-like activity, peroxidase-like activity, lactonase activity) which produces LPC. To study the possible role of PON1 in macrophage foam cell formation and atherogenesis we used macrophages from control mice, from PON1 knockout mice, and from PON1 transgenic mice. Furthermore, we analyzed PON1-treated macrophages and PON1-transfected cells to demonstrate the contribution of PON1 to the attenuation of macrophage cholesterol and oxidized lipid accumulation and foam cell formation. PON1 was shown to inhibit cholesterol influx [by reducing the formation of oxidized LDL (Ox-LDL), increasing the breakdown of specific oxidized lipids in Ox-LDL, and decreasing macrophage uptake of Ox-LDL]. PON1 also inhibits cholesterol biosynthesis and stimulates HDL-mediated cholesterol efflux from macrophages. PON2 and PON3 protect against oxidative stress, with PON2 acting mainly at the cellular level. Whereas serum PON1 and PON3 were inactivated under oxidative stress, macrophage PON2 expression and activity were increased under oxidative stress, probably as a compensatory mechanism against oxidative stress. Intervention to increase the paraoxonases (cellular and humoral) by dietary or pharmacological means can reduce macrophage foam cell formation and attenuate atherosclerosis development.
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PMID:Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. 1545 71

Peroxidases figure prominently in biology and contribute significantly to cell biology, host defense against infection, and pathogenesis of several inflammatory diseases. These varied and diverse aspects of peroxidase biochemistry and its clinical implications will be the subjects of in-depth analysis at the 4th International peroxidase meeting held in Kyoto. Specific topics range from the molecular basis of peroxidase structure and function to the clinical consequences of autoantibodies generated against myeloperoxidase (MPO), the peroxidase present in circulating neutrophils. Consideration of novel aspects of peroxidase biology, both unanticipated biochemical properties of MPO and the potential role of MPO in the pathogenesis of inflammatory diseases such as atherosclerosis, will also be included. In addition to peroxidases, the newly expanded family of NADPH oxidases will be discussed. We hope that this collection of scientists who share a common interest in peroxidase biology but each possess expertise in distinctly different aspects of the subject will provide a setting for spirited discussion and a lively exchange of views to yield advances in understanding and to create new applications of those insights to benefit clinical medicine, agriculture and industry.
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PMID:Contribution of peroxidases in host-defense, diseases and cellular functions. 1550 51

Our earlier studies have shown that some steroids increase myeloperoxidase enzyme (MPO) release from human granulocytes, and that MPO plasma levels are significantly lower in postclimacteric people. Moreover, we have proven that MPO inhibits production of atherogenic free radical superoxide anion and MPO-inhibitors increase superoxide release. The aim of the present study was to investigate the effect of MPO-inhibitors on the early phase of aortic atherosclerosis, namely the extent of intimal plaques and the thickening of the medial layer. Adult male rabbits were fed with lipid rich food (cholesterol: 1.3%, peanut oil: 8%) for 8 weeks. During this period MPO-inhibitors were also given (4-aminobenzoicacid-hydrazide/ABAH/-13.3 mg/kg/day or indometacin-5 mg/kg/day). All animals developed intimal lipid plaques (raised fatty streaks). The relative plaque-covered areas of the aortas were compared and the media thickness of the aorta was measured on plaque-free as well as plaque-containing areas. The medial smooth muscle density and peroxidase activity of the aortic media were also determined. The media thickness increased (p<0.05) in the cholesterol+ABAH as well as in the cholesterol+indometacin groups up to 375.7 (+/-60.5) and 442.5 (+/-123.4) microm, respectively, compared to the control group (cholesterol feeding alone) where it measured only 308.4 (+/-51.67) microm. The medial peroxidase activity decreased significantly in the indometacin treated group and showed a decreasing tendency using ABAH. In parallel to this there was a tendency of increase in the relative plaque covered areas. The smooth muscle density showed no significant modifications, while inhibitors of the MPO seemed to enhance aortic medial thickness, i.e. the grade of a pre-atherosclerotic lesion, in our animal model. Collectively, the anti-atherogenic effect of certain steroid hormones might be realized through the impact on MPO activity.
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PMID:Effect of inhibitors of myeloperoxidase on the development of aortic atherosclerosis in an animal model. 1576 97

Previous studies showed that subclinical hypothyroidism (SH) was associated with cardiovascular disorders, such as endothelial dysfunction, atherosclerosis and myocardial dysfunction. Only one study investigated left ventricular (LV) function using pulsed tissue Doppler echocardiography (TDE) in patients with SH. However, no study has used this technique in the identification of right ventricular (RV) function in these patients. We aimed to investigate the effect of SH on RV and LV function using TDE technique. The present study included 36 newly diagnosed SH patients and 28 healthy controls. For each subjects, serum free T3 (FT3), free T4 (FT4), total T3 (TT3), total T4 (TT4), TSH, peroxidase antibody (TPOab) and thyroglobulin antibody (TGab) levels were measured, and standard echocardiography and TDE were performed. In patients with SH, TSH levels were significantly higher, and TPOab and TGab levels were significantly higher when compared to healthy controls. TDE showed that the patients had significantly lower early diastolic mitral and tricuspid annular velocity (Ea) and early/late (Ea/Aa) diastolic mitral and tricuspid annular velocity ratio (p<0.05, p<0.05 and p<0.001, p<0.001, respectively), and significantly longer isovolumetric relaxation time (IRT) of left and right ventricles (p<0.001 and p<0.001, respectively). However, Aa, Sa, and isovolumetric contraction time (ICT) and ET (ejection time) of left and right ventricle did not significantly differ (p=ns for all). In addition, a negative correlation between TSH and TD-derived tricuspid Ea velocity and Ea/Aa ratio, and a positive correlation between TSH and IRT of right ventricle were observed. Our findings demonstrated that SH is associated with impaired RV diastolic function in addition to impaired LV diastolic function.
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PMID:Evaluation of right and left ventricular function using pulsed-wave tissue Doppler echocardiography in patients with subclinical hypothyroidism. 1627 66


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