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)

A relationship is described between H. pylori infection and diseases localized beyond the gastrointestinal tract, for example: atherosclerosis, stenocardia, cerebral stroke, chronic urticaria, rosacea, hemicrania and in, children with height deficit or anaemia, caused by iron deficiency. Two cases of sideropenic anaemia in children resistant to oral iron are presented. Gastrointestinal tract symptoms were not observed and most probably the reason for anaemia was H. pylori infection. The first 14 years old patient with normal menstrual periods had been treated for four months by oral iron, without any effect (Hgb 10.2 g%, Fe 36.8%, ferritin < 10.8 mg%). On endoscopy of upper gastrointestinal tract there were macroscopic typical changes of H. pylori infection in antrum part of the stomach. On histological examination of biopsy segments inflammation of stomach mucosa in average intensification and H. pylori infection was confirmed. Recovery caused normalization of iron in the organism and of erythrocyte morphology. There was no recurrence of anaemia in long-term observation of the girl. A 14 years old boy treated without success for severe sideropenic anaemia (Hgb 7.1 g%), with positive family history (father has gastric ulcer). In spite of lack of gastrointestinal tract symptoms, on endoscopy there were features of chronic active hemorrhagic inflammation of stomach mucosa with H. pylori infection. Oral iron and effective eradication (proton pump inhibitor, amoxycillin, clarithromycin), achieved normalization of morphological changes. Recurrence of anaemia has not been observed.
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PMID:[Helicobacter pylori infection as a cause of sideropenic anaemia resistant to treatment - own observation]. 1682 22

Inflammation and immune activation are crucially involved in the pathogenesis of atherosclerosis and cardiovascular disease. Accordingly, markers of inflammation such as fibrinogen, ferritin, C-reactive protein or neopterin are found in patients with vascular diseases, correlating strongly with the extent of disease and predicting disease progression. Neopterin formation by human monocyte-derived macrophages and dendritic cells is induced by the pro-inflammatory cytokine interferon-gamma, which is released by activated T-lymphocytes. Human macrophages are centrally involved in plaque formation, and interferon-gamma and macrophages are also of importance in the development of oxidative stress for antimicrobial and antitumoural defence within the cell-mediated immune response. Interferon-gamma also stimulates the enzyme indoleamine-2,3-dioxygenase, which degrades tryptophan to kynurenine. Again, macrophages are the most important cell type executing this enzyme reaction, but also other cells like dendritic cells, endothelial cells or fibroblasts can contribute to the depletion of tryptophan. Likewise, enhanced tryptophan degradation was reported in patients with coronary heart disease and was found to correlate with enhanced neopterin formation. In chronic diseases such as in cardiovascular disease, biochemical reactions induced by interferon-gamma may have detrimental consequences for host cells. In concert with other pro-inflammatory cytokines, interferon-gamma is the most important trigger for the formation and release of reactive oxygen species (ROS). Chronic ROS-production leads to the depletion of antioxidants like vitamin C and E and glutathione, with a consequence that oxidative stress develop. Oxidative stress plays a major role in the atherogenesis and progression of cardiovascular disease, and it may also account for the irreversible oxidation of other oxidation-sensitive substances like B-vitamins (e.g. folic acid and B12). They are essential cofactors in homocysteine-methionine metabolism. Associations between moderate hyperhomocysteinaemia and cellular immune activation are found in several diseases including coronary heart disease, and data indicate that hyperhomocysteinaemia may develop as a consequence of immune activation. Homocysteine accumulation in the blood is established as an independent risk factor for cardiovascular disease. Homocysteine itself has the capacity to further enhance oxidative stress. Interferon-gamma appears to be a central player in atherogenesis and in the development and progression of cardiovascular disease. Anti-inflammatory and immunosuppressive treatment (e.g. with non-steroidal anti-inflammatory drugs or statins) may among other consequences, also contribute to a slow-down of the adverse effects of interferon-gamma.
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PMID:Crucial role of interferon-gamma and stimulated macrophages in cardiovascular disease. 1684 38

The effect of increased iron stores on the progression of atherosclerosis and endothelial health remains inconclusive. This study was designed to evaluate the relationship between hemochromatosis genotypes, serum ferritin levels and presymptomatic vascular abnormalities in a cohort of healthy subjects. Carotid intima-media thickness (CIMT) and brachial flow-mediated vasodilation (FMD) were assessed by high-resolution ultrasound in 907 male (47 +/- 10 years) participants enrolled in the Firefighters and their Endothelium (FATE) study. Analyses of the hemochromatosis C282Y, H63D and S65C alleles were simultaneously determined by a single nucleotide polymorphism (SNP) primer extension method. It was found that brachial FMD was not related to serum ferritin or hemochromatosis genotype status. The presence of a hemochromatosis-associated genotype (n = 18) or heterozygosity for the C282Y genotype (n = 98) was not associated with an increased mean CIMT. After adjustment for conventional risk factors, serum ferritin was also not associated with mean CIMT. In conclusion, neither ferritin nor a hemochromatosis genotype was related to brachial endothelial function or carotid atherosclerosis. The present study does not support the hypothesis that mild to moderately increased iron stores are associated with enhanced atherosclerosis risk.
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PMID:The effect of iron status on vascular health. 1688 38

The oxidative modification of low-density lipoproteins (LDL) plays a central role in the initiation and acceleration of atherosclerosis. Iron plays a part in the formation of highly toxic free radicals such as hydroxide and superoxide anions, which can induce lipid peroxidation. We investigated whether serum iron status was associated with circulating oxidized LDL (oxLDL) levels in type 2 diabetic patients, in whom oxidative stress and susceptibility to lipid oxidation were supposedly increased. Serum ferritin levels were significantly correlated with plasma oxLDL concentrations in both male and female patients (p<0.02 and p<0.05, respectively). No correlation was detected between ferritin and LDL-cholesterol (LDL-C) concentrations despite the close correlation between LDL-C and oxLDL concentrations (p<0.0001). Stepwise regression analysis showed that ferritin concentration was an independent positive determinant of oxLDL level, in addition to triglyceride concentration, body mass index and sex. This is the first report to show that serum ferritin is associated with circulating oxLDL levels in patients with type 2 diabetes. Further work is required to establish a causative link between iron excess and the development of diabetic vascular complications.
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PMID:Association between serum ferritin and circulating oxidized low-density lipoprotein levels in patients with type 2 diabetes. 1690 60

Heme toxicity contributes to the pathogenesis of chronic inflammatory diseases, atherosclerosis, and hemolysis associated vasculopathy. Macrophage clearance of cell free hemoglobin (Hb) is thus an essential homeostatic function of these cells. We examined the transcriptional response of human PBMC derived macrophages to Hb by gene array analysis. The observed noninflammatory macrophage response was characterized by induction of an antioxidative and antiinflammatory gene expression pattern with most prominent induction of the inducible heme oxygenase (HO-1). The metabolically active Hb-CD163-HO-1 pathway resulted in synthesis of ferritin-1 of the antioxidative and antiinflammatory end products linked to heme breakdown by HO-1. This response was mediated by the Hb scavenger receptor CD163 and heme and was not related to Hb mediated depletion of reduced glutathione. In contrast to other cellular responses induced by CD163, there was no role of protein phosphorylation dependent CD163 signaling in the protective macrophage response to Hb. Instead, CD163 acted as an Hb transporter, which undergoes constitutive and ligand independent internalization and recycling between the cell surface and early endosomes. The expression of CD163 and HO-1 in macrophages of neovascularized atherosclerotic lesions suggests that the pathway described herein is active in vivo. Noninflammatory Hb clearance and intimately linked HO-1 expression may provide the long sought-after explanation for the antiinflammatory activity associated with CD163-positive macrophages.
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PMID:Constitutive endocytosis of CD163 mediates hemoglobin-heme uptake and determines the noninflammatory and protective transcriptional response of macrophages to hemoglobin. 1706 96

This exploratory substudy of The Iron (Fe) and Atherosclerosis Study (FeAST) compared baseline inflammatory markers, including cytokines, C-reactive protein (CRP), and ferritin, in subjects with peripheral arterial disease (PAD) taking statins with subjects with PAD who were not taking statins. Inflammatory markers in the serum of 47 subjects with PAD not taking statins and a healthy cohort of 21 medication-free men were compared with 53 PAD subjects taking statins at entry to the FeAST. Healthy subjects demonstrated lower levels of tumor necrosis factor (TNF)-R1, interleukin-6 (IL-6), and CRP. TNF-alpha R1 averaged 2.28 ng/mL versus 3.52 ng/mL, p = .0025; IL-6 averaged 4.24 pg/mL versus 16.61 pg/mL, p = .0008; and CRP averaged 0.58 mg/dL versus 0.92 mg/dL, p = .0192. A higher level of IL-6 was observed in PAD statin takers versus PAD subjects not taking statins: 19.47 pg/mL versus 13.24 pg/mL, p = .0455. As expected, total cholesterol and low-density lipoprotein levels were lower in the statin-treated group, p = .0006 and p = .0001, respectively. No significant differences in inflammatory cytokines were detected for varying doses of simvastatin. Additionally, no significant differences in inflammatory biomedical markers were found in subjects with PAD alone compared with those with concomitant coronary artery disease (CAD). Unexpectedly, serum inflammatory cytokine IL-6 levels were significantly higher in PAD subjects receiving statins. There was no difference in measured inflammatory markers in PAD subjects with concomitant CAD.
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PMID:Statins and biomarkers in claudicants with peripheral arterial disease: cross-sectional study. 1702 9

Several studies showed that carotid atherosclerosis and stiffness are independent prognostic factors of cardiovascular morbidity and mortality in the general population and in end-stage renal disease patients. However, the impact of established risk factors on carotid structural and elastic properties in non-diabetic elderly hemodialysis patients with negative history for cardiovascular disease has not been fully elucidated. In this paper, we investigated the effect of established and potential risk factors on carotid atherosclerosis and stiffness. Thirty stable, non-symptomatic, non-diabetic patients, aged 65-years and older (mean age 71.4+/-4.15, range 65-79) on hemodialysis for more than 6 months, were included. All patients underwent B-mode ultrasonography of common carotid artery estimating intima-media wall thickness and wall-to-lumen ratio bilaterally and checking for the presence of plaques. Carotid elasticity was evaluated by compliance, distensibility, and the incremental elastic modulus (Einc), whereas systemic arterial stiffening was evaluated by the augmentation index provided by tonometry of radial artery. Our results showed that presence of carotid plaques and wall thickening were frequent findings in this population (76% and 73.3%, respectively) and they were positively associated with fibrinogen (P<0.005), diastolic blood pressure (P<0.004), visceral obesity (P<0.001) and bio-intact PTH (i-PTH) (P=0.03). Overall, systemic and carotid stiffness were strongly correlated with hs-CRP (P=0.018), serum ferritin (P=0.02) with age (P=0.03), lipids (P=0.03) and i-PTH (P=0.05). In conclusion, our findings show that stiffening and atherosclerosis in non-symptomatic elderly HD patients are very common and they are related not only to hemodynamic changes (diastolic blood pressure), inflammation (hs-CRP, fibrinogen, ferritin) or metabolic dysfunction (increased i-PTH, abnormal lipid profile), but also to abnormal fat deposition (increased waist to hip ratio and waist circumference). Considering the high morbidity and mortality of elderly patients, close monitoring of these parameters could be useful to prevent cardiovascular events.
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PMID:Atherosclerotic risk factors and carotid stiffness in elderly asymptomatic HD patients. 1708 15

Oxidative stress and inflammation are common features and major mediators of atherosclerosis in end-stage renal disease (ESRD). Available evidence for oxidative stress in ESRD is indirect and based on accumulation of byproducts of interactions of reactive oxygen species (ROS) with various molecules. Inflammation is a major cause of oxidative stress. To explore the direct link between oxidative stress and inflammation in ESRD, we studied leukocyte integrin expression and ROS production in 18 ESRD patients and 18 controls. ESRD patients showed elevated plasma malondialdehyde (MDA) and increased superoxide and hydrogen peroxide (H(2)O(2)) production by granulocytes and monocytes before dialysis. Hemodialysis resulted in a further rise in plasma MDA and H(2)O(2) production by granulocytes and monocytes. Surface expression of Mac-1 (CD11b and CD18) on granulocytes and monocytes was significantly increased (denoting cell activation) in ESRD patients. Granularity of granulocytes was significantly reduced before dialysis and declined further after dialysis. The magnitude of ROS production by granulocytes and monocytes was directly related with CD11b expression as well as plasma ferritin and parathyroid hormone levels and was inversely related to protein catabolic rate. Thus, this study provides direct evidence of spontaneous leukocyte activation and increased ROS generation (hence the link between oxidative stress and inflammation) in ESRD patients.
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PMID:Spontaneous leukocyte activation and oxygen-free radical generation in end-stage renal disease. 1713 29

The association between iron, an oxidant catalyst, and atherosclerosis is controversial. In particular, it is unknown whether: (1) stored iron, namely serum ferritin, is correlated with catalytic iron and oxidant damage of human atherosclerotic plaques; (2) catalytic iron is related to oxidative injury within such plaques; (3) plaque oxidant burden is associated with the severity of atherosclerosis. Thus, we assessed low molecular weight iron (LMWI), which represents the metal catalytically active form, together with fluorescent damage products of lipid peroxidation (FDPL) and lipid hydroperoxides (LOOH), in 38 atherosclerotic plaques surgically removed from 38 patients who had undergone selective carotid endarterectomy. In each patient, the levels of serum ferritin were measured and correlated with those of plaque LMWI and lipoperoxides by the Spearman rank correlation test with Spearman rank correlation coefficient (r(S)) calculation. Moreover, in patients selected from the same study population, we compared plaque analyte levels between two groups with different severity of atherosclerotic carotid stenosis, i.e., <90% (group A, n = 25) or > or =90% (group B, n = 13), and between another two groups without (group C, n = 27) and with (group D, n = 11) associated contralateral carotid stenosis > or =50%, indicative of "extensive" and more severe atherosclerotic disease. In group A patients, serum ferritin was directly and significantly correlated with plaque LMWI (r(S) = 0.46, P < 0.025) and FDPL (r(S) = 0.58, P < 0.005), while its correlation with plaque LOOH, albeit direct, did not attain statistical significance. Moreover, a direct and significant relationship was evident between the plaque content of LMWI and that of both FDPL (r(S) = 0.61, P < 0.0025) and LOOH (r(S) = 0.51, P < 0.025), suggesting a prooxidant role of catalytic iron within human atherosclerotic plaques. Considering the 13 patients of group B, a positive and significant correlation was observed between the levels of serum ferritin and those of plaque LMWI (r(S) = 0.83, P < 0.0001); on the other hand, serum ferritin, as well as plaque LMWI, showed no significant correlation with either plaque FDPL or LOOH, conceivably reflecting the small number of patients belonging to group B. Finally, plaque LMWI, FDPL, and LOOH content was significantly higher in group B than in group A, and in group D than in group C. These data suggest a role for catalytic iron in atherosclerotic plaque oxidation and in the severity of atherosclerosis, which appears indeed associated with plaque oxidant burden.
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PMID:Association of body iron stores with low molecular weight iron and oxidant damage of human atherosclerotic plaques. 1727 81

The authors performed a case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) Study to determine the association between plasma ferritin level and risk of type 2 diabetes mellitus. Persons with incident cases of type 2 diabetes diagnosed over an average follow-up period of 7.9 years (n = 599) were compared with a random sample of the cohort (n = 690). After adjustment for age, gender, menopausal status, ethnicity, center, smoking, and alcohol intake, the hazard ratio for diabetes, comparing the fifth quintile of ferritin with the first quintile, was 1.74 (95% confidence interval: 1.14, 2.65; p-trend < 0.001). After further adjustment for body mass index and components of the metabolic syndrome, the hazard ratio was 0.81 (95% confidence interval: 0.49, 1.34; p-trend = 0.87). From a causal perspective, there are two alternative interpretations of these findings. Elevated iron stores, reflected in elevated plasma ferritin levels, may induce baseline metabolic abnormalities that ultimately result in diabetes. Alternatively, elevated ferritin may be just one of several metabolic abnormalities related to the underlying process that ultimately results in diabetes, rather than a causal factor for diabetes. Longitudinal studies with repeated measurements of glucose and iron metabolism parameters are needed to establish the role of iron stores and plasma ferritin in diabetes development.
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PMID:A prospective study of plasma ferritin level and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. 1728 22


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