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)

Epidemiologic studies have shown a significant relationship between elevated plasma levels of Lp(a) and increased risk of cardiovascular events; however, the mechanisms by which elevated Lp(a) levels produce this increased risk are not known. To test the hypothesis that high Lp(a) levels might contribute to the development of subclinical atherosclerosis, we examined the influence of Lp(a) levels on early functional and structural atherosclerotic vascular changes. Flow-mediated (endothelium-dependent) and nitrate-mediated (smooth muscle-dependent) arterial dilations were measured by high-resolution ultrasound in 241 normal healthy subjects (aged 15 to 69 years; 116 men). In addition, carotid artery intima-media thickness was measured by ultrasound in 71 subjects. Plasma Lp(a) was measured using a 2-sided immunoradiometric assay (cohort median, 10 mg/dL; interquartile range, 3.9 to 24.4 mg/dL). In these subjects, there were no significant relationships between Lp(a) and arterial endothelial function, smooth muscle responses, or carotid wall thickness (P>0.25). By contrast, other lipid risk factors, such as LDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratio, were significantly correlated with abnormal arterial function and structure (P</=0.01). These data suggest that elevated Lp(a) levels do not confer cardiovascular risk by contributing to the early functional or structural changes of atherosclerosis.
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PMID:Effect of Lp(a) on the early functional and structural changes of atherosclerosis. 1019 27

Morphofunctional reorganization was studied of endothelium during the stage of formation of alimentary atherosclerosis and in experimental hyperadrenalinemia using transmission electronic microscopy and histochemistry together with silver nitrate impregnation of aortal endothelial monolayer. Certain morphofunctional equivalents have been established for the vascular wall exposure to the above factors, indicative of their unequalability and possibility of potentiation under combination. In both cases, an interrelationship similar in character has been shown between intensity of the endothelial reciprocal response and its regional morphofunctional features.
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PMID:[The characteristics of the morphofunctional restructuring of the aortic endothelium in food-related atherosclerosis and hyperadrenalinemia]. 1020 51

This study examined whether lysophosphatidylcholine (lysoPC), an atherogenic lipid, may stimulate production of O2*-, in cultured human endothelial cells. Production of O2*- was detected by bis-N-methylacridinium nitrate (lucigenin)-elicited chemiluminescence. LysoPC was found to induce burst production of O2*-, peaked at 2-4 min after the stimulation, in intact endothelial cells. LysoPC also stimulated NADH-dependent production of O2*- in particulate fraction of the cells, and the action of lysoPC was inhibited by diphenyliodonium. The results suggested that lysoPC stimulated production of O2*- partly through membrane-associated NADH-dependent O2*- production systems.
Atherosclerosis 1999 Mar
PMID:Burst production of superoxide anion in human endothelial cells by lysophosphatidylcholine. 1020 96

Clinical effects of recombinant human erythropoietin (rHuEPO) such as thrombosis, convulsions, hyperviscosity, hypertension, and angiogenic effect in culture cells have been described. We studied the rHuEPO effect on endothelial damage markers and endothelial function markers: tissue-type plasminogen activator (t-PA), nitrate (NO3), thrombomodulin (TM), and von Willebrand factor (vWF). Twenty-six peritoneal dialysis patients treated with rHuEPO and 19 controls were included. The study design for rHuEPO patients consisted of four periods: long-term treatment (rHuEPO-1); 2 months of withdrawal (rHuEPO-2); and 4 months on 5000 IU/week rHuEPO subcutaneously, with markers being measured after 2 months (rHuEPO-3) and after 4 months (rHuEPO-4). After 2 months of rHuEPO withdrawal, a decrease in hemoglobin level appeared (11+/-1.8 g/dL to 9.2+/-1.5 g/dL, p < 0.01). After rHuEPO reintroduction, this value reached 10.6+/-1.5 g/dL at two months, and 11.1+/-1.4 g/dL at four months. A significant increase in t-PA ratio was observed from two months without rHuEPO to two months on rHuEPO, returning to previous values after four months. Similarly, TM increased for patients with creatinine clearances (CrC) < 5 mL/min. No changes in the higher-than-normal plasma vWF levels were found during the various periods. A statistically significant lower value was found in controls compared with rHuEPO-4 patients. A statistically significant increase in NO3 levels was observed in the pre-venous occlusion (VO) test immediately after the re-introduction of rHuEPO. This increment returned to prior values four months after rHuEPO was reintroduced. Our results show that rHuEPO treatment causes an increase in some endothelial damage markers (TM, t-PA) and modifies endothelial function markers (t-PA ratio, NO3). These changes might favor thrombosis and atherosclerosis.
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PMID:Effects of recombinant human erythropoietin on functional and injury endothelial markers in peritoneal dialysis patients. 1040 11

Protein nitration and lipid peroxidation are implicated in the pathogenesis of atherosclerosis; however, neither the cellular mediators nor the reaction pathways for these events in vivo are established. In the present study, we examined the chemical pathways available to monocytes for generating reactive nitrogen species and explored their potential contribution to the protein nitration and lipid peroxidation of biological targets. Isolated human monocytes activated in media containing physiologically relevant levels of nitrite (NO(2)(-)), a major end product of nitric oxide ((*)NO) metabolism, nitrate apolipoprotein B-100 tyrosine residues and initiate LDL lipid peroxidation. LDL nitration (assessed by gas chromatography-mass spectrometry quantification of nitrotyrosine) and lipid peroxidation (assessed by high-performance liquid chromatography with online tandem mass spectrometric quantification of distinct products) required cell activation and NO(2)(-); occurred in the presence of metal chelators, superoxide dismutase (SOD), and scavengers of hypohalous acids; and was blocked by myeloperoxidase (MPO) inhibitors and catalase. Monocytes activated in the presence of the exogenous (*)NO generator PAPA NONOate (Z-[N-(3-aminopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2- diolate) promoted LDL protein nitration and lipid peroxidation by a combination of pathways. At low rates of (*)NO flux, both protein nitration and lipid peroxidation were inhibited by catalase and peroxidase inhibitors but not SOD, suggesting a role for MPO. As rates of (*)NO flux increased, both nitrotyrosine formation and 9-hydroxy-10,12-octadecadienoate/9-hydroperoxy-10,12-octadecadieno ic acid production by monocytes became insensitive to the presence of catalase or peroxidase inhibitors, but they were increasingly inhibited by SOD and methionine, suggesting a role for peroxynitrite. Collectively, these results demonstrate that monocytes use distinct mechanisms for generating (*)NO-derived oxidants, and they identify MPO as a source of nitrating intermediates in monocytes.
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PMID:Formation of nitric oxide-derived oxidants by myeloperoxidase in monocytes: pathways for monocyte-mediated protein nitration and lipid peroxidation In vivo. 1055 42

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (statins) may enhance vascular endothelial function independent of their cholesterol lowering effect. To test this hypothesis, we surveyed two groups of patients (age 55+/-7, mean+/-SD) with coronary artery disease that were matched for age, blood pressure and serum lipid levels. Group 1 comprised 23 men without lipid-lowering medication and Group 2 included 22 patients with ongoing HMG CoA reductase inhibitor medication. Flow-mediated (endothelium-dependent) arterial dilatation (FMD) and nitrate-mediated (smooth muscle dependent) dilatation (NMD) were measured in the brachial artery using high resolution ultrasound. FMD was considerably higher in group 2 (4.3+/-2.6 vs. 2.6+/-2.8%; P<0.05). In multivariate regression model, statin use was the only significant (P<0.05) predictor of FMD. In all subjects, FMD correlated with statin dose (P<0.05 for trend). NMD was non-significantly higher in group 2 (11.4+/-5.0 vs. 9.0+/-4.2%, P=0. 08). We conclude that patients with established coronary artery disease on HMG CoA reductase inhibitor therapy have better vascular endothelial function than similar patients without the medication. These data provide further support for the idea that HMG CoA reductase inhibitors enhance endothelial function independent of their lipid-lowering effects. This may suggest that these drugs could be beneficial in secondary prevention of coronary artery disease regardless of the serum cholesterol concentration.
Atherosclerosis 1999 Dec
PMID:HMG CoA reductase inhibitors are related to improved systemic endothelial function in coronary artery disease. 1055 8

To examine whether or not the levels of NOx (nitrite; NO2- and nitrate; NO3-) in coronary circulating blood reflect endothelial dysfunction due to coronary atherosclerosis, NOx levels in plasma obtained from ostium of left coronary artery and coronary sinus of patients who complained of chest pain were evaluated in relation to their coronary angiographic findings. Prior to the study, a HPLC-Griess system for NOx measurement was critically evaluated. This system has a detection limit of 0.1 microM of NO2- and NO3- by 10 microl of loading and was able to distinguish a difference of 0.1-0.2 microM of these substances. Heparin (1 U/10 microl) did not affect the detective and discriminative abilities. NO3- difference, calculated from sino-arterial difference of NO3-, was almost zero (-0.2 +/- 0.2 microM) in patients with either normal coronary arteries or mild organic coronary stenosis (< or = 20% narrowing), while a significant negative value (-5.9 +/- 1.7 microM) was obtained from patients with significant stenosis (> or = 70% narrowing) in the left coronary arteries. These results demonstrate reliable ability on the HPLC-Griess system in evaluating NO2- and NO3- in biological samples, and that the negative NO3- difference through coronary circulation may reflect endothelial dysfunction in the patients with coronary atherosclerosis with severe organic stenosis.
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PMID:Negative NO3- difference in human coronary circulation with severe atherosclerotic stenosis. 1066 13

To evaluate the influence of atherosclerosis on the global production of NO, we studied the effect of a 0.3% cholesterol-enriched diet on urinary nitrate excretion in rabbits during 69 weeks. To examine whether the inducible nitric oxide synthase (iNOS) present in atherosclerotic lesions could participate in NO excretion, hypercholesterolemic rabbits were treated chronically with the selective iNOS inhibitor, N-iminoethyl-L-lysine (L-NIL; 5 mg/kg/day). Urinary nitrate excretion was higher in hypercholesterolemic than in control rabbits throughout the study period and decreased progressively with time in both groups; L-NIL had no significant effect on urinary nitrate excretion. These data illustrate that systemic NO production is enhanced in hypercholesterolemia and that iNOS, present within the plaque, might not participate in this enhanced NO production.
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PMID:Urinary nitrate excretion in cholesterol-fed rabbits: effect of a chronic treatment by N-iminoethyl-L-lysine, a selective inhibitor of inducible nitric oxide synthase. 1067 37

Dehydroepiandrosterone (DHEA) is speculated to have an antiatherosclerotic effect, although the mechanism of action remains unclear. The objective of the current study was to determine whether the antiatherosclerotic effect of DHEA is related to its conversion to estrogen and to define the role of nitric oxide (NO) in the antiatherosclerotic effect of DHEA. Forty-eight oophorectomized rabbits were divided into 5 groups and fed the following diets for 10 weeks: group 1, a regular rabbit diet plus 1% cholesterol (a high-cholesterol diet [HCD]); group 2, an HCD plus 0.3% DHEA; group 3, an HCD plus 0.3% DHEA and fadrozole (2.0 mg x kg(-1) x d(-1)), a specific aromatase inhibitor; group 4, an HCD plus 17beta-estradiol (20 microg x kg(-1) x d(-1)); and group 5, a regular diet. Atherosclerotic lesions, lipid deposition in aortic vessels, and basal and stimulated NO release were measured in the aforementioned groups of rabbits. NO release was measured by using an NO-selective electrode as well as by measuring vascular responses and the plasma NO metabolites nitrite and nitrate. The plasma total cholesterol level was increased, but there were no significant differences in lipid profile in the 4 groups of rabbits that were fed the HCD. The area occupied by atherosclerosis in the thoracic aorta was diminished by approximately 60% in the DHEA-treated rabbits (group 2) compared with the HCD group of rabbits (group 1); there was a corresponding 80% decrease in the estradiol group (group 4) but only a 30% decrease in the DHEA plus fadrozole group (group 3). In the aortas of rabbits from groups 1 and 3, the acetylcholine-induced and tone-related basal NO-mediated relaxations were diminished compared with those of the controls (group 5). However, these relaxations were restored in the aortas of group 2 and 4 rabbits, and an increase in NO release was observed in groups 2 and 4 compared with groups 1 and 3, as measured by an NO-selective electrode. Injection of neither solvent (20% ethanol/distilled water) nor fadrozole significantly affected the atherosclerotic area or the NO-related responses described above. We conclude that approximately 50% of the total antiatherosclerotic effect of DHEA was achieved through the conversion of DHEA to estrogen. NO may also play a role in the antiatherosclerotic effect of DHEA and 17beta-estradiol.
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PMID:Dehydroepiandrosterone retards atherosclerosis formation through its conversion to estrogen: the possible role of nitric oxide. 1071 4

There is a large body of literature describing the causative role of oxidative stress mediated by increased levels of reactive oxygen species in the pathogenesis of cardiovascular disease such as atherosclerosis, hypertension, and restenosis after angioplasty. The positioning of a soft silicone collar around the rabbit carotid artery elicits intimal thickening. The findings from recent studies demonstrated that both intimal thickening and atherosclerosis lead to synthesis of inducible nitric oxide synthase, resulting in abundant amounts of nitric oxide. We investigated the effects of collaring and nicardipine treatment on the activities of antioxidant enzymes, superoxide dismutase and catalase, and total nitrite/nitrate levels, stable products of nitric oxide. Placing the collar increased the total nitrite/ nitrate levels and decreased superoxide dismutase activity in collared arteries. Treatment with nicardipine (20 mg/kg/day, s.c.) prevented enhanced nitric oxide degradation without affecting superoxide dismutase and catalase activities. Our results suggest that enhanced nitric oxide production and superoxide anion are generated in response to the collaring, resulting in oxidative stress within the segment in this model.
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PMID:Antioxidant enzyme activities and total nitrite/nitrate levels in the collar model. Effect of nicardipine. 1077 57


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