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)

Ultrafast computed tomography (CT) is a new method for detecting calcific lesions in the coronary arteries. The ability of CT to detect and quantify coronary artery atherosclerosis in children and young adults at risk for malignant atherogenesis was evaluated. A total of 11 consecutive familial hypercholesterolemic (FH) homozygotes (3 to 37 years old) participated. Untreated total cholesterol concentrations were 488 to 1277 mg/dL (12.7 to 33.2 mmol/L). Angiography detected significant lesions in 7 of 11 patients. CT detected calcific atherosclerosis in all 9 of the patients older than 12 years of age, including all those with angina. CT was more sensitive in detecting aortic root and coronary ostial lesions, where atherosclerosis first appears in homozygous FH. The volume of calcification (in cubic millimeters) correlated with the severity and duration of the hypercholesterolemia (r = .62, P < .05) as well as with the presence of angina (P < .05). All patients with angina (7 of 7) had > 150 mm3 of calcified volume, whereas only 1 of 4 asymptomatic patients had a volume score > 150 mm3. We conclude that (1) coronary and aortic calcium phosphate deposits are common in young FH homozygotes; (2) these deposits are associated with the presence of angiographic stenoses, as has been seen in adults with coronary atherosclerosis; and (3) aortic calcific deposits are more common than calcific coronary lesions.
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PMID:Detection and quantitation of calcific atherosclerosis by ultrafast computed tomography in children and young adults with homozygous familial hypercholesterolemia. 801 61

In the present study possible antiatherogenic effects of dietary garlic were investigated in an experimental model which consists in the deendothelialisation by ballooning of the a. carotis communis of rats. 3 experimental groups were established: group I received a standard diet; the diet of group II was supplemented with 2% cholesterol and group III received 2% cholesterol and 5% dried garlic powder. Four weeks after ballooning plasma cholesterol, the average thickness of the neointima as well as the DNA content and the expression of collagens type I, III and IV in the ballooned arterial segment were determined. Furthermore, the specific activities of the enzymes glutathione peroxidase, glutathione disulfide reductase, glutathione-S-transferase and glucose 6 phosphate dehydrogenase were measured in homogenates of liver, heart and aorta. Hypercholesterolemia induced by cholesterol-feeding (group II 92 +/- 18 mg/100 ml) was significantly reduced by garlic (group III 53 +/- 19 mg/100 ml). Only little effects of garlic were seen in inhibiting neointima after ballooning. However, significant effects were found in protecting the enzymes of the glutathione dependent peroxide detoxification system, which is strongly impaired under hypercholesterolemia. Generally a normalisation, in some cases even an improvement beyond that, of the enzyme activities occurred in the garlic treated group. This indicates that in the model of atherosclerosis used here garlic is effective in lowering plasma cholesterol and in improving peroxide detoxification, however, it has only little influence on the wound healing reaction and does not significantly inhibit the development of intimal thickenings after ballooning.
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PMID:Effects of dietary garlic supplementation in a rat model of atherosclerosis. 802 33

Low-density lipoproteins (LDL) oxidized by oxygen radicals are a potent atherogenic stimulus. Chemically modified LDL are internalized by macrophages via a specific cell surface receptor that was termed the scavenger receptor, and could induce foam cell transformation. Post-translational nonenzymatic glycosylation of low density lipoprotein (LDL) occurs in vivo in diabetic patients. Glycosylated LDL (glcLDL) is degraded by macrophages in part by the classic LDL-receptor and in part by the scavenger receptor. This latter mechanism may contribute to the formation of foam cells and acceleration of atherosclerosis in diabetes mellitus. Oxygen free radicals (ORs) could induce LDL peroxidation and subsequent formation of foam cells. Glycosylation may alter protein conformation. A free radical is any chemical species that has an unpaired electron. This property renders it highly chemically reactive. When a radical reacts with a non radical another free radical is generated. This characteristic enables radicals to trigger chain reactions. Oxygen radicals are: superoxide anion (.O2-), hydroxyl radical (.OH) and hydrogen peroxide (H2O2). Thus, the aim of this study was to investigate whether glcLDL are susceptible to peroxidative modification by ORs. GlcLDL was prepared incubating LDL with 40 mM glucose in sterile phosphate-buffer-EDTA 1 mM for 10 days at 37 degrees C. Control LDL (cLDL) was similarly incubated with buffer but without glucose. After this preparation both forms of LDL were oxidized by CuSO4 (15 microM for 20 hours at 37 degrees C) or by xanthine/xanthine oxidase (X:2 mM/XO: 100 mU for 20 hours at 37 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The peroxidation of human glycosylated low-density lipoproteins is mediated by the superoxide radical: the protective effects of superoxide dismutase]. 808 16

Excess free radicals are linked to many diseases, including aging, atherosclerosis, and cancer. Previously, we have shown that MA-631 (a complex herbal mixture) inhibits human low-density lipoprotein (LDL) oxidation and may play a role in prevention of atherosclerosis. In this study we further evaluated the in vivo and in vitro antioxidant activity of MA-631. Both the alcoholic and aqueous extracts of MA-631 inhibited enzymatic- and nonenzymatic-induced rat liver microsomal lipid peroxidation in a concentration-dependent manner. The thiobarbituric acid-reactive substances (TBARS) values (nmol malondialdehyde (MDA)/mg microsomal protein) were 1.43 +/- 0.18 for microsomes alone (baseline for enzymatic system), 19.63 +/- 2.50 for microsomes + reduced nicotinamide adenine dinucleotide phosphate (NADPH) (oxidation without inhibitor), 9.89 +/- 1.41 for heated microsomes (baseline for nonenzymatic system), and 27.15 +/- 0.08 for microsomes + ascorbate (oxidation without inhibitor). The concentrations (micrograms/2 ml) of MA-631 which produced 50% inhibition (IC50) of enzymatic- and non-enzymatic-induced lipid peroxidation were 15.2 +/- 2.0 and 17.0 +/- 2.6, respectively, for the aqueous extract, and 4.3 +/- 0.8 and 6.4 +/- 1.2, respectively, for the alcoholic extract. A 2% MA-631 (w:w) supplemented diet fed to rats for three weeks inhibited in vivo, toluene-induced microsomal lipid peroxidation in the brain, kidney, liver, and heart. These results imply that MA-631 may be useful in the prevention of free radical-linked diseases.
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PMID:In vitro and in vivo inhibition of microsomal lipid peroxidation by MA-631. 809 Aug 22

Patients with primary hyperparathyroidism have increased bone turnover, but it is less well documented how brief periods of excess parathyroid hormone (PTH) (endogenous or exogenous) affect bone metabolism. In the present double blind study, we examined the effect of either ethylenediaminetetraacetatic acid (EDTA) or placebo on serum levels of PTH and biochemical markers of bone turnover in 15 women and 39 men (aged 41 to 81 years) suffering intermittent claudication due to atherosclerosis. Disodium EDTA was administered as 20 repeated infusions of 3 grams during a period of 5-9 weeks. Serum calcium and serum phosphate decreased following treatment (p < 0.001) and remained unchanged in the placebo group. However, the differences between the groups were insignificant (ANOVA p = 0.13 and p < 0.10, respectively). PTH increased 2 1/2 fold following EDTA treatment (p < 0.001, ANOVA). The change in serum PTH was inversely correlated with the change in serum calcium (r = -0.53, p < 0.01). In the EDTA group, urinary hydroxyproline/creatinine and calcium/creatinine increased after treatment (ANOVA p < 0.001 and p < 0.05, respectively). Serum bone alkaline phosphatase decreased significantly in the EDTA group immediately after treatment (p < 0.001, ANOVA) and returned to baseline level at three months while only an insignificant decrease in serum osteocalcin was seen following treatment. We conclude that EDTA treatment increases endogenous PTH secretion considerably and leads to increased bone resorption. However, no changes in osteoblastic markers indicating increased activation of bone remodeling could be demonstrated. Our findings support that chelation therapy with EDTA is accompanied by bone loss.
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PMID:Effects of intravenous EDTA treatment on serum parathyroid hormone (1-84) and biochemical markers of bone turnover. 829 6

The glycogen storage disorders (GSD)-I, -III, -VI and -VIII are associated with hypertriglyceridaemia or mixed hyperlipidaemia which poses the question whether these patients have an increased risk for atherosclerosis. The atherogenicity of triglycerides has remained controversial, while increased plasma cholesterol levels are generally accepted as a significant risk factor for coronary heart disease. However, clinical data show that one has to differentiate between metabolic conditions where triglycerides are atherogenic and those which are not significantly related to early onset of atherosclerosis but may cause other disorders such as pancreatitis. Among the disorders of carbohydrate metabolism patients with diabetes mellitus frequently have enhanced plasma triglycerides associated with a higher risk for coronary heart disease, while patients with certain types of glycogen storage disease have high triglyceride levels but do not seem to have an enhanced risk for atherosclerosis. Here we have compared the biochemical abnormalities and the atherogenic risk of three different disorders of glucose metabolism including GSD-I (glucose-6-phosphatase deficiency), favism (glucose-6-phosphate dehydrogenase deficiency), and diabetes mellitus which are related to either hyper- or hypolipidaemia. The available data indicate that glucose-6-phosphate (Glc-6-P) is a central molecule in cellular glucose metabolism which critically influences pentose phosphate cycle activity and, via NADPH2-generation, regulates glutathione peroxidase activity for radical detoxification and also cholesterol and triglyceride synthesis. Radical detoxification is a major protective factor for cell membrane integrity and together with an appropriate renewal of membrane lipids may protect against the development of atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose-6-phosphate: a key compound in glycogenosis I and favism leading to hyper- or hypolipidaemia. 831 30

Nepsilon-(Carboxymethyl)lysine (CML) is an advanced glycation end product formed on protein by combined nonenzymatic glycation and oxidation (glycoxidation) reactions. We now report that CML is also formed during metal-catalyzed oxidation of polyunsaturated fatty acids in the presence of protein. During copper-catalyzed oxidation in vitro, the CML content of low density lipoprotein increased in concert with conjugated dienes but was independent of the presence of the Amadori compound, fructoselysine, on the protein. CML was also formed in a time-dependent manner in RNase incubated under aerobic conditions in phosphate buffer containing arachidonate or linoleate; only trace amounts of CML were formed from oleate. After 6 days of incubation the yield of CML in RNase from arachidonate was approximately 0.7 mmol/mol lysine compared with only 0.03 mmol/mol lysine for protein incubated under the same conditions with glucose. Glyoxal, a known precursor of CML, was also formed during incubation of RNase with arachidonate. These results suggest that lipid peroxidation, as well as glycoxidation, may be an important source of CML in tissue proteins in vivo and that CML may be a general marker of oxidative stress and long term damage to protein in aging, atherosclerosis, and diabetes.
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PMID:The advanced glycation end product, Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. 862 37

Limited data are available on the determinants of homocysteinemia or the association between plasma homocysteine (Hcy) levels and prevalent cardiovascular disease (CVD) in maintenance dialysis patients. We assessed etiology of renal failure, residual renal function and dialysis adequacy-related variables, and vitamin status, as determinants of fasting total plasma homocysteine (Hcy) in 75 maintenance dialysis patients. We also assessed the potential interactive effect on plasma Hcy of folate status and a common mutation (ala to val; homozygous val-val frequency approximately 10%) in methylenetetrahydrofolate reductase (MTHFR), a folate-dependent enzyme crucial for the remethylation of homocysteine (Hcy) to methionine. Lastly, we evaluated whether the Hcy levels differed amongst these patients in the presence or absence of prevalent CVD, after adjustment for the traditional CVD risk factors. Fasting total plasma Hcy, folate, pyridoxal 5'-phosphate (PLP; active B6), B12, creatinine, glucose, total and HDL cholesterol levels, and presence of the ala to val MTHFR mutation were determined, and clinical CVD and CVD risk factor prevalence were ascertained. General linear modelling/analysis of covariance revealed: (1) folate status and serum creatinine were the only significant independent predictors of fasting Hcy; (2) there was a significant interaction between presence of the val mutation and folate status, i.e., among patients with plasma folate below the median (< 29.2 ng/ml), geometric mean Hcy levels were 33% greater (29.0 vs. 21.8 microM, P = 0.012) in the pooled homozygotes (val-val) and heterozygotes (ala-val) for the ala to val mutation, vs. normals (ala-ala); (3) there was no association between prevalent CVD and plasma Hcy. Given potentially intractable survivorship effects, prospective cohort studies will be required to clarify the relationship between plasma Hcy or any putative CVD risk factor, and incident CVD in dialysis patients. If a positive association between plasma Hcy and incident CVD can be established in maintenance dialysis patients, the current data provide a rationale for additional folic acid supplementation in this patient population.
Atherosclerosis 1996 Jun
PMID:Folate status is the major determinant of fasting total plasma homocysteine levels in maintenance dialysis patients. 878 50

The concentration of homocysteine in plasma has been shown to be increased in renal failure, possibly contributing to the accelerated atherosclerosis observed in uraemic patients. The aim of the present study was to document the relationship between plasma total homocysteine (tHcy) concentrations and glomerular filtration rates (GFR) in highly selected patients, with renal function ranging from normal to dialysis dependency. GFR was defined as the plasma clearance of iohexol; a more accurate method than the creatinine-based estimations applied in previous studies. Plasma tHcy concentrations were highly correlated to GFR (r = -0.70, p < 0.0001) and were significantly increased already in moderate renal failure. According to a multiple regression analysis, GFR and red cell folate concentrations independently predicted plasma tHcy concentrations, whereas those of serum creatinine, plasma pyridoxal-5-phosphate, urine albumin and urine alpha-1-microglobulin (a marker of tubular damage) did not. Thus, GFR seems to be a better determinant of plasma tHcy concentration than serum creatinine concentration. Plasma total cysteine and total cysteinylglycine concentrations followed the same pattern as those of tHcy.
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PMID:The effect of reduced glomerular filtration rate on plasma total homocysteine concentration. 885 Jan 71

The oxidative modification of low-density lipoprotein by macrophages may be an important mechanism in the pathogenesis of atherosclerosis. The human monocytic leukaemic cell line THP-1, when stimulated with phorbol ester, shares many properties with human monocyte-derived macrophages. Oxidation of LDL by these cells was characterised by depletion of alpha-tocopherol, increases in thiobarbituric acid reactive substances and increases in electrophoretic mobility. The LDL particles were also converted to a form which increased accumulation of cholesteryl esters within macrophages. The oxidative mechanism appeared to be dependent upon the presence of thiols in the cellular medium. Oxidation of LDL by THP-1 macrophages, and production of thiols by these cells, were dependent upon the presence of L-cystine in the medium. Furthermore, cellular oxidation of LDL could be partially mimicked by the addition of cysteine to Hams F10 medium. Macrophage-independent oxidation of LDL, mediated by the addition of copper ions, was inhibited by cystine and cysteine in phosphate buffered saline, but not in Hams F10 medium. The glutathione content of THP-1 macrophages was also dependent upon the presence of cysteine or cystine in the medium, but inhibition of glutathione synthesis by buthionine sulfoximine did not prevent the production of thiols or the oxidation of LDL by THP-1 macrophages.
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PMID:Human (THP-1) macrophages oxidize LDL by a thiol-dependent mechanism. 784 39


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