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)

Plasma levels of neopterin were determined in patients with different clinical stages of atherosclerosis. Non-hospitalized patients with atherosclerosis had serum and plasma neopterin levels within the normal range of the assay (6 +/- 2 nM). These values were not significantly different from those reported for healthy blood donors (5 +/- 2 nM). In contrast, about 50% (29 out of 61) of hospitalized patients undergoing conservative or surgical therapy had neopterin plasma levels, which exceeded the normal range (greater than 10 nM) up to 10-fold. The two groups differ on a significance level of P less than 0.01. For further evaluation hospitalized patients were subgrouped according to neopterin levels. In the subgroup with elevated neopterin levels patients with higher Frederickson types of atherosclerosis were overrepresented compared to patients with normal neopterin levels. Type 4 differed significantly from patients without pathological changes of lipoprotein (P less than 0.05). Only 3 patients suffered from minimal skin necrosis, two of them had elevated neopterin levels. Significantly more patients with peripheral artery occlusions had elevated neopterin levels than patients with occlusions of central arteries (P less than 0.05). All other criteria used for comparison (sex, age, smoking, antioxidant status, diabetes, hypertension, adipositas, hyperuricemia) did not vary significantly in both subgroups. These data indicate that neopterin plasma levels might be a valuable parameter in activity staging and therapeutic follow up of atherosclerotic patients. Additionally, an involvement of the nonspecific immune system in atherogenesis is suggested by the increased plasma neopterin concentrations.
Atherosclerosis 1991 Aug
PMID:Elevated serum neopterin levels in atherosclerosis. 179 48

Activation of T-cells and macrophages may play a role in the pathogenesis of atherosclerosis. Therefore, serum concentrations of the immune activation markers neopterin and soluble interleukin-2 receptor were compared with routine laboratory parameters, candidate risk variables and degree of carotid atherosclerosis. Study subjects were 561 individuals (293 men and 268 women) aged between 50 and 79 years who were enrolled in a cross-sectional community based study (Ischemic Heart Disease and Stroke Prevention Study, Bruneck, Italy). Extent of carotid atherosclerosis was quantitated by an ultrasound B-mode procedure based scoring system. Detailed physical examination and quantification of laboratory and candidate risk variables were performed. By univariate as well as multivariate statistical analyses, serum concentrations of neopterin but not soluble interleukin-2 receptor were significantly higher in subjects with carotid atherosclerosis (men, 8.5 +/- 2.7 nmol/l neopterin; women, 9.6 +/- 3.3) than in those without (men, 6.7 +/- 2.3, P < 0.0001; women, 7.5 +/- 2.3, P < 0.0001). The data show that the macrophage-derived immune activation marker neopterin is closely correlated with the extent of carotid atherosclerosis. Chronic activation of immune cells, preferentially of macrophages, may play a key role in atherogenesis and/or progression of atherosclerosis.
Atherosclerosis 1994 Apr
PMID:Increased concentrations of neopterin in carotid atherosclerosis. 806 Mar 86

To clarify relationships between the (endothelial vasodilatory and vasoconstrictive function) and leukocyte inflammatory mediators in subjects with asymptomatic atherosclerosis, we measured (intraplatelet cyclic 3',5'-guanosine monophosphate [cGMP] and cyclic 3',5'-adenosine monophosphate [cAMP]), plasma endothelin (ET-1), and plasma neopterin in 197 subjects with asymptomatic atherosclerosis (median age 63 years, range 49-69 years). We measured neutrophil protease 4 (NP4), tumor necrosis factor (TNFmu), soluble tumor necrosis factor receptor-1 (sTNFR-1), and neutrophil gelatinase associated lipocalin (NGAL) in 152 of the 197 subjects. Intraplatelet cGMP correlated inversely with plasma ET-1 (r=-0.22; p=0.01), which confirms earlier in vitro data of the inhibitory effect of ET-1 on NO production and/or the cGMP mediated inhibitory effect of NO on ET-1 production. Plasma neopterin as well as NP4 correlated directly with intraplatelet cGMP (r=0.24; p<0.01 and r=0.33; p<0.001, respectively). Intraplatelet cAMP correlated directly with plasma TNFmu (r=0.17; p<0.05) and sTNFR-1 (r=0.20; p<0.05). The relationship between leukocyte derived inflammatory mediators and intraplatelet cyclic nucleotides suggest an antiaggregating effect of leukocytes upon platelets, which may constitute a negative feedback mechanism that inhibits platelet activation during the atherosclerotic inflammatory process.
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PMID:Endothelial derived vasoactive factors and leukocyte derived inflammatory mediators in subjects with asymptomatic atherosclerosis. 985 70

Release of inflammatory mediators from leukocytes and endothelial release of vasoactive factors are both important in the pathogenesis of atherosclerosis. To evaluate the concentrations of a specific marker for macrophage activation, neopterin, and the potent endothelial derived vasoconstrictive peptide endothelin-1 (ET-1), during the acute and chronic stages of cerebral ischemia, plasma concentrations of neopterin and ET-1 were measured in 59 patients with acute cerebral infarction or transient ischemic attack (median age 73 years, range 43-93, 27 men) and after a 1-year follow-up in 57/59 (97%) of patients. Plasma neopterin was higher at follow-up (6.3 nmol/L [3.7-21.6] vs 5.6 nmol/L [3.5-17.2]; p < 0.05) than at the acute stage, whereas the plasma ET-1 concentration was unchanged. Plasma concentrations of both neopterin and ET-1 correlated directly with age both in the acute stage (r = 0.42 and r = 0.35, respectively; p < 0.01) and after follow-up (r = 0.34; p < 0.05 and r = 0.27; p = 0.05, respectively). In conclusion, plasma neopterin increased after acute cerebral ischemia, indicating chronic inflammatory activity and continuous macrophage activation in ischemic cerebrovascular diseases.
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PMID:Increasing plasma neopterin and persistent plasma endothelin during follow-up after acute cerebral ischemia. 992 83

Systemic serum markers of inflammation are elevated in diseases due to atherosclerosis, but have not been associated with the extent of atherosclerotic disease. We examined the role of neopterin, a byproduct of activated macrophage metabolism, in patients with unstable angina. Baseline neopterin samples and clinical histories were obtained in 52 patients admitted with unstable angina pectoris. Coronary angiograms of 27 patients were reviewed using Sullivan's method to assess the total atherosclerotic burden in the coronary arteries. Twenty-six of the 52 patients were eventually diagnosed with a non-Q-wave acute myocardial infarction (AMI) and had higher neopterin levels (10.1 +/- 6.7 vs 7.2 +/- 4.0 nmol/L, p = 0.06) than patients with a final diagnosis of unstable angina. Patients with neopterin >8.7 were more likely to be diagnosed with a non-Q-wave AMI (75% vs 39%, p = 0.035) and were more likely to have significantly more severe and extensive angiographically determined atherosclerosis than patients with low neopterin levels. Neopterin levels correlated with the score of atherosclerotic extension (Spearman's rank correlation coefficient 0.4807, p = 0.034). This study demonstrates a correlation between immune cell activation and the extent of angiographically determined atherosclerosis and the degree of myocardial ischemia.
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PMID:Serum neopterin levels and the angiographic extent of coronary arterial narrowing in unstable angina pectoris and in non-Q-wave acute myocardial infarction. 1007 53

Plasma concentration of markers of inflammation are increased in patients with atherosclerosis. However, it is unclear whether the pattern and magnitude of this increase vary with the site and extent of disease. In 147 patients undergoing semiquantitative coronary angiography, we measured the acute-phase reactants C-reactive protein (CRP) or serum amyloid A (SAA); the proinflammatory cytokine interleukin 6 (IL-6); the active and total fractions of the anti-inflammatory cytokine transforming growth factor-beta (TGF-beta); the macrophage activation marker neopterin; and the infection marker procalcitonin. Compared with 62 patients without either coronary artery disease (CAD) or peripheral artery disease (PAD), 57 patients with CAD but no PAD showed greater median CRP (0. 4 versus 0.2 mg/dL, P=0.004) and IL-6 (3.8 versus 1.6 pg/mL, P=0. 007) levels and a lower level of active-TGF-beta (57 versus 100 ng/mL, P=0.038). Moreover, CRP, IL-6, and neopterin levels showed a positive and the active TGF-beta level a negative correlation with the extent of coronary atherosclerosis. Compared with these 57 patients with CAD alone, 15 patients with PAD and CAD had higher median levels of SAA (17 versus 7 mg/mL, P=0.008), IL-6 (12 versus 4 pg/mL, P=0.002), neopterin (14 versus 11 mg/dL, P=0.006), and total TGF-beta (11834 versus 6417 ng/L, P=0.001). However, these strong univariate associations of markers of inflammation and atherosclerosis were lost in multivariate analysis once age, sex, and high density lipoprotein cholesterol or fibrinogen were taken into account. Increased plasma levels of CRP, SAA, IL-6, TGF-beta, neopterin, and procalcitonin constitute an inflammatory signature of advanced atherosclerosis and are correlated with the extent of disease but do not provide discriminatory diagnostic power over and above established risk factors.
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PMID:Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries. 1052 64

Leukocyte-derived inflammatory mediators and endothelial production of vasoconstrictive factors, such as endothelin-1, and vasodilatory and platelet anti-aggregatory factors, such as nitric oxide (NO) and prostacyclin (PGI2), may have a role in the pathogenesis of atherosclerosis. In this study we evaluated whether insulin affects the monocyte-derived inflammatory mediator neopterin and endothelin- in plasma (p), and NO and PGI2 mediators cyclic 3'-5' guanosine monophosphate (cGMP) and cyclic 3'-5' adenosine monophosphate (cAMP) in platelets. P-neopterin was measured by enzyme linked immunosorbent assay (ELISA), and p-endothelin-1, intraplatelet cAMP and cGMP were measured by radioimmunoassay (RIA) before and after euglycaemic hyperinsulinaemic clamping in 51 healthy postmenopausal women aged 53-54 years. "Placebo clamping" with NaCl infusion was performed in a subgroup of 5/51 women. During euglycaemic hyperinsulinaemic clamping, p-endothelin-1 decreased (from 3.3+/-0.2 pg/ml to 2.4+/-0.2 pg/ml; p<0.01), whereas p-neopterin (from 5.0+/-1.1 nmol/l to 6.2+/-1.4 nmol/l; p<0.001) and both intraplatelet cGMP (from 0.61+/-0.03 to 0.68+/-0.03 pmol/10(9) platelets; p<0.05) and cAMP (from 4.00+/-0.14 to 4.76+/-0.20 pmol/10(9) platelets; p<0.001) increased. Increases in cGMP (from 0.79+/-0.05 to 1.07+/-0.15 pmol/10(9) platelets; p = 0.14) and cAMP (from 4.76+/-0.15 to 5.52+/-0.36 pmol/10(9) platelets; p = 0.08) also occurred during NaCl infusion, whereas neopterin and endothelin-1 values were unchanged. In conclusion, insulin administration was associated with decreasing p-endothelin-1 levels and increasing levels of p-neopterin and intraplatelet cyclic nucleotides in accordance with vasodilatation and monocyte activation.
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PMID:Increasing neopterin and decreasing endothelin-1 in plasma during insulin infusion in women. 1061 52

Some infectious agents may contribute to atherosclerosis by maintaining a heightened state of inflammatory response. Although the risk for atherosclerosis was associated with elevated plasma levels of endotoxin, it is difficult to firmly establish what place endotoxin assumes in the etiology of this disease. As the ability for endotoxin to promote disease may depend on its ability to initiate an inflammatory response, it may be controlled by additional regulatory factors. We measured plasma levels of endotoxin and serum levels of neopterin and soluble interleukin-2 receptor in a random population of 402 men and women, 50-79 years old at the 1990 baseline evaluation (Bruneck Study). End point of the prospective survey was incident (early) atherosclerosis in the carotid arteries as assessed with duplex ultrasound. Subjects with high endotoxin levels (90th percentile) in combination with low neopterin or soluble interleukin-2 receptor levels (below median) did not differ from those with low endotoxin in their risk of incident atherosclerosis. The risk associated with high endotoxin, however, was markedly elevated in subjects with high (above median) neopterin or soluble interleukin-2 receptor levels. The study provides epidemiological evidence that the atherogenic potential of endotoxemia is affected by concomitant immune activation.
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PMID:The role of immune activation in endotoxin-induced atherogenesis. 1171 90

Inflammation plays a key role in the pathogenesis of atherosclerosis. In coronary artery disease (CAD), the release of different cytokines activates cellular defense. Infiltration of neutrophils and monocytes/macrophages is detected in the vessel wall in patients with CAD. Macrophages activated by interferon gamma synthesize metalloproteinases and neopterin, a pteridin derivative that has been used as an immune marker. To determine neopterin levels in patients with chronic CAD and acute coronary syndromes, the authors studied 116 subjects: 1) 25 consecutive patients (18 men, 7 women; mean age 68.5 +/- 14.3, range 40 to 86 years) with unstable angina or acute myocardial infarction (AMI); 2) 31 consecutive patients (25 men, 6 women; mean age 64 +/- 12.7, range 47 to 83 years) with signs and symptoms of clinically stable CAD; and 3) 60 consecutive healthy blood donors (38 men, 22 women; mean age 54.4 +/- 6.23, range 44 to 66 years). Neopterin levels were determined with a commercially available enzyme-linked immunosorbent assay method. In patients with unstable angina and AMI before thrombolytic therapy, neopterin levels were not significantly different from levels in patients with stable CAD (5.97 +/- 1.4 versus 7.84 +/- 3.56 nmol/L; P = 0.15). Neopterin levels in both patient groups did not significantly differ from levels in control subjects (P > 0.1). Neopterin levels in patients with unstable angina and AMI were measured four times during a 72-hour period. The lowest value was observed at baseline and differed significantly from values after 72 hours (P < 0.001; 5.97 +/- 1.4 versus 9.25 +/- 2.36). Neopterin levels after 72 hours were also significantly different from initial values in patients with stable CAD (P < 0.001). There was no correlation between neopterin and creatine kinase (CK) levels, CK-MB isoenzyme, or troponin I as markers for the extent of the myocardial injury during the observation period. These data do not support previous reports of higher baseline levels of serum neopterin in patients with unstable angina or AMI compared with patients with chronic, stable CAD and healthy controls. Neopterin as a marker of macrophage activation is significantly increased in patients with AMI and unstable angina shortly after the onset of symptoms (after a period of 72 hours), supporting the hypothesis of monocyte and macrophage activation in patients with an acute coronary syndrome or AMI.
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PMID:Serum neopterin and activity of coronary artery disease. 1197 9

Low density lipoprotein (LDL) oxidation within the artery wall likely represents a key event in the formation of atherosclerotic lesions. Oxidatively modified LDL particles exert chemotactic properties on macrophages, and the uncontrolled uptake of modified LDL by macrophages leads to the formation of lipid-loaded foam cells, a hallmark of early stage atherosclerosis. Human macrophages stimulated by interferon-gamma generate reactive oxygen species (ROS), neopterin, and 7,8-dihydroneopterin. Higher concentrations of neopterin were found in atherosclerosis, and earlier studies have provided evidence that these neopterin derivatives are able to interfere with reactive species. We therefore investigated whether they also modulate LDL oxidation mediated by Cu(II) and/or peroxynitrite (ONOO-). By means of UV-absorption recording the formation of conjugated dienes in the course of lipid oxidation as well as by measuring the relative electrophoretic mobility of oxidized LDL, we found that neopterin is capable of enhancing ONOO- - as well as Cu(II)-mediated LDL oxidation, whereas 7,8-dihydroneopterin mainly protects LDL from oxidation. However, in case of Cu(II)-mediated LDL oxidation, an initial prooxidative effect of 7,8-dihydroneopterin could be observed. We hypothesize that 7,8-dihydroneopterin may chemically reduce Cu(II) to Cu(I) thereby increasing its oxidative capacity. After total reduction of Cu(II), excess 7,8-dihydroneopterin may block the oxidative potential of Cu(I) and thus decrease the oxidation of LDL. These findings confirm the general behavior of pteridines in redox processes and suggest an in vivo contribution to the process of LDL oxidation.
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PMID:Neopterin and 7,8-dihydroneopterin interfere with low density lipoprotein oxidation mediated by peroxynitrite and/or copper. 1215 May 39


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