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)

We studied factors that may add to the high risk of atherosclerosis in kidney transplant recipients. Plasma lipoprotein concentrations and parameters of low density lipoprotein (LDL) oxidation were determined in 19 clinically stable kidney recipients and 19 healthy controls. Plasma triglycerides and total cholesterol were increased in the patients. High density lipoprotein-cholesterol (HDL-c) was in the normal range. The mean LDL diameter was smaller in patients than in controls (236.5 +/- 7.3 A vs. 247.8 +/- 11.6 A, P < 0.002), which was due to a higher frequency of the LDL subclass pattern B in the patients than in controls (58% vs. 28%). The lag time of copper-induced in vitro LDL oxidation was shorter in patients than in controls (101 +/- 23 min vs. 148 +/- 81 min, P = 0.02). The titer and concentration of autoantibodies against malondialdehyde-modified (MDA-LDL) determined by ELISA were higher in the patients than in the controls. This difference was found in both IgG (titer + 9%, concentration + 75%; P < 0.05) and IgM (titer + 35%, concentration + 102%; P < 0.001). Based on these results, we propose that there is in vitro and in vivo evidence of enhanced LDL oxidation in patients post-renal transplantation. This might represent one cause for the clinical finding of advanced atherosclerosis in these patients.
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PMID:Increased low density lipoprotein oxidation in stable kidney transplant recipients. 882 34

Diabetes mellitus is known as an independent risk factor in atherosclerosis. Among the prominent biochemical changes that occur in diabetic state, are the enhanced formation of advanced glycosylation end products (AGE) (especially linked to albumin and collagen) and the impaired oxidative-antioxidative balance. Previously, we have shown that AGE-albumin (AGE-Alb) significantly alters the physico-chemical characteristics of low density lipoproteins of normal (nLDL) and diabetic (dLDL) subjects. In this study we tried to establish if incubation of nLDL or dLDL, with AGE-Alb in autoxidative conditions, modifies the rate and/or the pathway of their uptake by macrophages. To this purpose, nLDL and dLDL were exposed to AGE-Alb, and after re-isolation and radiolabeling the lipoproteins were incubated with U937 or peritoneal macrophages (for various time and concentrations), in the absence or presence of different competitors (native LDL, acetylated LDL, AGE-Alb, mannan) or cytochalasin D. As controls, nLDL and dLDL, maintained in similar conditions, but without AGE-Alb, were used. The results showed that preincubation for 24 h and 72 h with AGE-Alb augmented the macrophage uptake for both nLDL and dLDL (1.7-fold). Either pre-incubated or not with AGE-Alb, dLDL was taken up at a constantly higher rate than nLDL; the difference appeared more prominent at 72 h (1.5 vs. 4 micrograms LDL protein/mg cell protein). The increased level of glycation of native dLDL as compared to native nLDL (266 +/- 35 vs. 160 +/- 24 mmol HMF/mol apoB) as well as of the lipid peroxides (1.34 +/- 0.47 vs. 0.3 +/- 0.09 nmol MDA/mg apoB) could account for the greater uptake of dLDL at any preincubation time. Competition experiments indicated that, generally, incubation with AGE-Alb diminished the apo B100,E receptor-mediated uptake in favour of 'scavenger' receptor pathway and phagocytosis. Macrophage uptake of AGE-Alb modified dLDL was reduced approximately 30% by native nLDL, approximately 70% by acetylated LDL and approximately 38% by cytochalasin D. Together, these data suggest that the consequence of the alterations induced by AGE-Albumin on LDL is the increased macrophage uptake, via non-saturable pathways, that ultimately may lead to accelerated formation of atherosclerotic plaques in diabetics.
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PMID:Increased macrophage uptake of irreversibly glycated albumin modified-low density lipoproteins of normal and diabetic subjects is mediated by non-saturable mechanisms. 887 21

Low density lipoproteins (LDL) from hypertensive patients are more prone to in vitro oxidation and undergo a more pronounced oxidation in vivo. Due to the pro-atherogenic activity of oxidatively modified LDL, the correlation between the carotid intima-media thickening (IMT) and the markers of in vivo LDL oxidation was investigated in hypertensive patients. A cross-sectional study on 101 normocholesterolemic patients with newly diagnosed and untreated essential hypertension was performed. The occurrence of in vivo LDL oxidation was evaluated by measuring the titers of autoantibodies against Cu(2+)-oxidised LDL (oxLDL) and malondialdehyde-derivatised LDL (MDA-LDL). The extent and degree of atherosclerosis and the IMT were measured by means of carotid and femoral ultrasonography with a duplex scanner equipped with a high resolution probe. We did not find significant correlations between in vivo LDL oxidation parameters and the extent of atherosclerotic lesion in the entire group of hypertensive patients. However, a significant direct correlation was detected between the carotid IMT and the titer of autoantibodies against both oxLDL and MDA-LDL in hypertensive patients without advanced atherosclerotic plaques. The results obtained support the hypothesis that enhanced LDL oxidation may be one of the pathophysiological events related to the formation and progression of early atherosclerotic lesions (IMT) in carotid arteries of hypertensive patients.
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PMID:Carotid intima-media thickening and in vivo LDL oxidation in patients with essential hypertension. 895 1

Numerous studies have indicated that oxidative modification of low-density lipoprotein(LDL) plays a critical role in the pathogenesis of atherosclerosis. Malondialdehyde-modified LDL(MDA-LDL) is one of the candidates which is the oxidative product of LDL. However, the existence of MDA-LDL in the circulation has been in dispute. Therefore, for the assessment of oxidized-LDL in human serum, we developed a sensitive enzyme-linked-immunosorbent assay(ELISA) for the detection of MDA-LDL. In our method, monoclonal antibody against MDA-LDL, ML25 was used. ML25 recognized MDA-LDL as well as MDA-modified proteins by a solid-phase competitive enzyme immunoassay. Therefore, to establish an ELISA method which is specific for detection of MDA-LDL, ML25 was combined with apoB-specific antibody (AB16) as the second antibody. Using this method, MDA-LDL was detectable in the sera of 314 healthy individuals. The concentration of MDA-LDL preferably ranged from 20 to 80 units/l when the absorbance with artificially prepared MDA-LDL at the concentration of 1 mg/l was defined as 1 unit/l. Furthermore, assays for lipoprotein subfractions separated by density-gradient ultracentrifugation revealed that MDA-LDL was mainly distributed in the LDL fraction as expected, and MDA-LDL/apoB ratio showed a peak at small, dense LDL fractions. This finding seems to be quite interesting since an elevated level of small, dense LDL has been reported to be associated with an increased risk of atherosclerosis. We concluded that our method is useful for specific detection of MDA-LDL in human serum and might be an elevation method for atherogenicity.
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PMID:[Determination of malondialdehyde-modified LDL(MDA-LDL) and its potential usefulness]. 902 42

Malondialdehyde-modified LDL(MDA-LDL) is one of the major oxidative LDL. MDA-LDL was determined by enzyme immunoassay in patients with complete and partial cholesteryl ester transfer protein(CETP) deficiency. Significantly increased serum MDA-LDL levels and MDA-LDL/apoB ratios in the LDL fraction were observed in patients with complete CETP deficiency but not for those with partial CETP deficiency. The present results may indicate that patients with complete CETP deficiency have a higher risk for atherosclerosis than those with partial CETP deficiency and normal.
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PMID:[Complete cholesteryl ester transfer protein deficiency increases oxidized-LDL in plasma]. 902 43

Oxidative modifications of lipoproteins could contribute to the development of atherosclerosis, but the influence of dietary fats on high density lipoprotein (HDL) oxidative modification is unknown. This study was designed to determine whether a diet rich in oleic acid could modulate the oxidative modification of HDL3. Twenty two healthy men were randomly placed on a 32-wk crossover study of an oleic acid rich diet supplied by a variant of sunflower oil vs a linoleic acid rich diet provided by conventional sunflower oil. Plasma HDL3 obtained after the diet rich in oleic acid showed a significantly higher oleic acid content in the phospholipid than lipoprotein isolated after the linoleic acid rich diet. HDL3 isolated after the oleic acid rich diet had lower values of thiobarbituric acid reactive substances (TBARS) than HDL3 obtained after the linoleic acid rich diet both for native (mean +/- SE; 0.24 +/- 0.02 vs 0.42 +/- 0.08 nmol MDA/mg protein; p < 0.01) and copper oxidized HDL3 (0.75 +/- 0.06 vs 0.95 +/- 0.07 nmol MDA/mg protein; p < 0.01). Indeed, TBARS for native HDL3 were negatively correlated with the oleic acid to linoleic acid ratio and positively with the percentage of linoleic acid in their phospholipids. Interestingly, HDL3 after both diets had similar antioxidant vitamins A and E content. HDL3 overall composition and fluidity were similar after the two diets. Moreover, HDL3 obtained after both diets produced identical [3H] free cholesterol efflux from human monocyte-derived macrophages (29%) and fibroblasts (26%). In conclusion, HDL3 rich in oleic acid was less easily oxidized regardless of the content of antioxidants such as vitamins A and E. Therefore, dietary monounsaturated fatty acid prevent the oxidative modification of lipoproteins.
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PMID:Oleic acid rich diet protects against the oxidative modification of high density lipoprotein. 903 43

Recently, involvement of remnant-like particle cholesterol (RLP-C) in atherosclerosis was reported, but this parameter has not been adequately investigated in hemodialysis (HD) patients. The present study investigated the relationship between the RLP-C level and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipid peroxides (malone dialdehyde, MDA), apolipoprotein (Apo) A-I, and ApoB. In addition, the fractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), LDL, and HDL in serum lipoproteins were determined by disk polyacrylamide gel electrophoresis. The relationship between the RLP-C level and three atherogenic indices was also studied. The RLP-C level in HD patients (8.2 +/- 6.7 mg/dl) was significantly higher than that in normal controls (2.7 +/- 1.3 mg/dl). The RLP-C level showed a significant positive correlation with the levels of TC, TG, LDL-C, MDA, ApoB, VLDL(%), and IDL(%), as well as a negative correlation with HDL(%). However, there was no correlation with age or the duration of HD. RLP-C also showed significant positive correlations with the (TC -HDL-C)/HDL-C ratio and the (VLDL + LDL)/HDL ratio, as well as a negative correlation with the ApoA-I/ApoB ratio. These results suggest that RLP-C may be a potential indicator of atherogenic risk in HD patients.
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PMID:Remnant-like particle cholesterol may indicate atherogenic risk in patients on chronic hemodialysis. 917 Dec 93

Oxidative modification of LDL is believed to be a crucial step in atherosclerosis. Thus, antioxidant vitamins may have a role in the prevention of coronary disease. We examined the cross-sectional association of serum vitamin levels, the susceptibility of LDL to hemin-induced oxidation (lag phase to conjugated diene formation), and the malondialdehyde-LDL (MDA-LDL) to native LDL radioactivity binding ratio with carotid intima-media thickness (IMT), a measure of asymptomatic early atherosclerosis. The participants in this observational study were 231 asymptomatic age-, sex-, race-, and field center-matched case-control pairs selected from the Atherosclerosis Risk in Communities (ARIC) study cohort on the basis of B-mode carotid artery ultrasonograms obtained from 1986 through 1989. Cases exceeded the 90th percentile of IMT, and control subjects were below the 75th percentile of IMT for all arterial segments. Biochemical analyses were performed on fasting frozen (-70 degrees C) serum specimens collected from 1990 through 1992. In conditional logistic regression adjusting for age, blood storage time, total cholesterol, and log-triglyceride concentrations, serum beta-cryptoxanthin and lutein plus zeaxanthin levels were inversely related to the extent of atherosclerosis (odds ratio [OR] per 1-SD increase: 0.75, 95% confidence interval [CI]: 0.59-0.94; and OR per 1-SD increase: 0.76, 95% CI: 0.59-0.95, respectively). Increases in alpha-carotene and lycopene were associated with nonsignificantly lower odds of being a case, whereas beta-carotene, retinol, and alpha-tocopherol were unrelated to IMT. Although not reaching statistical significance, the lag phase and autoantibodies against MDA-LDL were positively associated with asymptomatic atherosclerosis. After adjustment for potential confounders, only the inverse association of lutein plus zeaxanthin with asymptomatic atherosclerosis was maintained. This study supports a modest inverse association between circulating levels of some carotenoids, particularly lutein plus zeaxanthin, and carotid IMT. These findings suggest that these carotenoid compounds (regarded as biomarkers of fruit and vegetable intake) may be important in early stages of atherosclerosis.
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PMID:Association of serum vitamin levels, LDL susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis. A case-control study. The ARIC Study Investigators. Atherosclerosis Risk in Communities. 919 70

The present investigation was performed to clarify the effect of EPA on PGI2 production in vitro using cultured rat vascular smooth muscle cells (VSMC). To simulate in vivo conditions, a triacylglycerol (TG) emulsified form of EPA was used. An increase in EPA content was achieved without alteration of arachidonic acid concentration. These experiments clearly demonstrated that co-incubation of EPA-TG increased PGI2 production by cultured VSMC in a dose dependent fashion. Among polyunsaturated fatty acid TG examined (docosahexaenoic acid, linoleic acid, oleic acid and EPA), only EPA-TG was effective. Cyclooxygenase (COX) was activated, but neither phospholipase A2 nor PGI2 synthase activity was changed. EPA treatment did not alter the amount of COX-1 and COX-2 protein in VSMC. Addition of antioxidants, such as butylated hydroxytoluene or vitamin E, decreased MDA levels in the medium and cells and reversed the enhanced PGI2 production in EPA rich-VSMC. Therefore, the high polyunsaturation of EPA could generate low levels of lipid peroxides and thereby lead to activation of COX and an increased PGI2 production. Although EPA increased PGI2 production, only a negligible amount of PGI3 was produced by rat aortic tissues. Enhanced production of PGI2 might contribute to the anti-atherogenic effect of EPA.
Atherosclerosis 1997 Jun
PMID:Mechanisms of enhanced production of PGI2 in cultured rat vascular smooth muscle cells enriched with eicosapentaenoic acid. 919 75

Cardiovascular diseases represent the first cause of mortality in chronic renal failure patients treated by hemodialysis. Alterations in lipid metabolism and oxidative stress are recognized as vascular risk factors. Their corrections could be of interest for atherosclerosis prevention. In order to evaluate interest of an therapeutic intervention, we have analyzed oxidative metabolism in hemodialysis patients by determining the production of oxygen reactive species (ROS), the level of defense mechanisms, and the balance between nitric oxide (NO) and ROS, responsible for anti- or proxidant effects of NO. During dialysis sessions performed with cellulosic membrane (Cuprophan) an increase in hydroperoxide production by platelets was noted (12 HETE) (5.62 +/- 0.94 pg); similarly, superoxide anion (O2(0)-) production by monocytes (fluorescence index: 115 +/- 24) and by polynuclear cells (fluorescence index: 115 +/- 24) was enhanced. On the other hand, anti-oxidant defenses were significantly reduced with a decrease in RBC SOC activity (0.92 +/- 0.06 U/mg Hg) and in RBC vitamin E (0.7 +/- 0.07 mg/l) concentration. We have demonstrated a profound alteration in the L-arginine/NO pathway consequently to an accumulation of NO synthases inhibitors or activators. The necessity to reduce the production of ROS during dialysis sessions justifies the use of more biocompatible membranes, such as modified cellulosic or synthetic membranes, decreasing leucocyte activation. In addition, NO synthetase inhibitors can be preferentially eliminated by convection. Finally, a supplementation with an exogenous anti-oxidant, such as oral vitamin E (500 mg/day for 6 months) normalizes RBC vitamin E levels and concomitantly allows a decrease in MDA concentrations In conclusion, oxidative metabolism alterations observed in hemodialysis are multifactorial: preventive measures include the use of a more biocompatible material, the reequilibrium of the NO/ROS balance, and supplementation with exogenous anti-oxidants.
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PMID:[Oxidative stress and chronic renal insufficiency: what can be a prophylactic approach?]. 940 62


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