Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A method is described for the large scale preparation of reconstituted high density lipoproteins (rHDL) suitable for therapeutic use. Apolipoprotein A-I (apoA-I was isolated from precipitates obtained by cold ethanol fractionation of human plasma. This process includes several steps for virus removal and virus inactivation, among them pasteurization. Reconstitution of lipoprotein particles was performed by cholate dialysis using soybean phosphatidylcholine as the lipid source. An apoA-I:lipid ratio of 1:150 (mol:mol) was obtained. Redissolved rHDLs were disc-shaped particles resembling nascent HDL, as assessed by electron microscopy. The method was optimized for low content of free apoA-I protein as well as the low concentration of free lipid. The product was stabilized by lyophilization in the presence of sucrose. In vitro studies show potential effects it the prevention of gram-negative septic shock and in the inhibition of atherosclerosis.
 ...
PMID:Production and characterization of a reconstituted high density lipoprotein for therapeutic applications. 891 58

We investigated the injurious effects of reactive oxygen metabolites on the intestinal epithelium and the possible protective role played by two olive oil phenolic compounds, (3,4-dihydroxyphenyl)ethanol and (p-hydroxyphenyl)ethanol, using the Caco-2 human cell line. We induced oxidative stress in the apical compartment, either by the addition of 10 mmol/L H2O2 or by the action of 10 U/L xanthine oxidase in the presence of xanthine (250 micromol/L); after the incubation, we evaluated the cellular and molecular alterations. Both treatments produced significant decreases in Caco-2 viability as assessed by the neutral red assay. Furthermore, we observed a significant increase in malondialdehyde intracellular concentration and paracellular inulin transport, indicating the occurrence of lipid peroxidation and monolayer permeability changes, respectively. The H2O2-induced alterations were completely prevented by preincubating Caco-2 cells with (3,4-dihydroxyphenyl)ethanol (250 micromol/L); when the oxidative stress was induced by xanthine oxidase, complete protection was obtained at a concentration of polyphenol as small as 100 micromol/L. In contrast, (p-hydroxyphenyl)ethanol was ineffective up to a concentration of 500 micromol/L. Our data demonstrate that (3,4-dihydroxyphenyl)ethanol can act as a biological antioxidant in a cell culture experimental model and that the ortho-dihydroxy moiety of the molecule is essential for antioxidant activity. This study suggests that dietary intake of olive oil polyphenols may lower the risk of reactive oxygen metabolite-mediated diseases such as some gastrointestinal diseases and atherosclerosis.
 ...
PMID:The protective effect of the olive oil polyphenol (3,4-dihydroxyphenyl)-ethanol counteracts reactive oxygen metabolite-induced cytotoxicity in Caco-2 cells. 903 29

The effect of alcohol feeding on the development of atherosclerosis was investigated in low-density lipoprotein receptor gene-knockout (LDLR-/-) mice. Eight-week-old male mice were pair-fed atherogenic liquid diets containing ethanol at different levels (w/v; group A, 5%; group B, 2.5%; and group C, 0%). Tissue sections of the heart were stained with Oil Red O to examine for fatty lesions in proximal aorta. Results showed that the lesion size of group A was 70% smaller than group C after 6 weeks. By contrast, the lesion size of group B was not significantly different from that of group C. Serum high-density lipoprotein-apolipoprotein A1 (apo A1) A1 in LDLR-/- mice was suppressed by feeding the atherogenic diet, but the decrease was negated by alcohol (both groups A and B). The effectiveness of 5% alcohol to protect against atherosclerosis waned with time, but was still noticeable at 12 weeks, even though serum apo A1 remained high. Serum apolipoprotein E was increased by the high fat diet, but not altered by alcohol in the diet. Our data, therefore, show that: (1) alcohol-feeding impedes early atherosclerosis in LDLR-/- mice (this effect of alcohol is dose-dependent); (2) the protective effect of alcohol is not entirely attributable to an elevated serum high-density lipoprotein-apo A1; and (3) severe impairment of lipoprotein metabolism due to a lack of low-density lipoprotein receptors can eventually overwhelm the protective effect of alcohol against atherosclerosis.
Alcohol Clin Exp Res 1997 Feb
PMID:Alcohol feeding impedes early atherosclerosis in low-density lipoprotein receptor knockout mice: factors in addition to high-density lipoprotein-apolipoprotein A1 are involved. 904 67

Local delivery of pharmacological agents into the vessel wall has been extensively studied to prevent restenosis after coronary angioplasty. Alcohol solution was found to affect cellular responses to growth stimulation. This study was carried out to examine the effect of local delivery of alcohol solution on intimal proliferation following balloon injury. New Zealand white rabbits of 2-3 kg underwent balloon denudation of bilateral iliac arteries. Following denudation, 2 ml 10% or 15% alcohol solution was infused into one iliac arterial wall using a Wolinsky porous balloon catheter. The other iliac artery of the same animal received local delivery of normal saline and was used as the control. The animals were killed at 2 weeks. The neointimal areas of alcohol treated vascular segments were significantly less than those of control segments in both 10% (n = 10) and 15% (n = 11) groups (65 +/- 16 versus 113 +/- 20 x 10(3) microns2 in 10% group, P < 0.0001; 48 +/- 15 versus 107 +/- 10 x 10(3) microns2 in 15% group, P = 0.002). In order to determine the effect of alcohol solution on smooth muscle cell proliferation, a method of quantifying phenotypic conversion of smooth muscle cells was chosen. This consists of a measurement of volume fraction of the synthetic organelles (VFSO) of vascular smooth muscle cell profiles (SMC) using transmission electron micrographs taken in the animals killed at day 8. The VFSO of SMC of the control sites were significantly greater than those of paired 10% alcohol treated arteries in both intima (0.39 +/- 0.02 versus 0.21 +/- 0.01, P < 0.0001) and media (0.33 +/- 0.03 versus 0.19 +/- 0.02, P < 0.0001). Similar findings were noted in the 15% alcohol treated group. It is concluded that intramural alcohol delivery using porous balloon catheter is effective in reducing neointimal proliferation in rabbit iliac arteries after balloon injury. The mechanisms of action may involve direct inhibition of cellular responses to growth stimulation.
Atherosclerosis 1996 Dec 20
PMID:Local alcohol delivery may reduce phenotype conversion of smooth muscle cells and neointimal formation in rabbit iliac arteries after balloon injury. 912 12

There is accumulating evidence that estrogen replacement therapy protects against the development of coronary atherosclerosis and myocardial infarction in postmenopausal women. The mechanism of this protective effect is uncertain. The purpose of the present study was to determine whether 17 beta-estradiol acutely modifies vascular smooth muscle contractile responses to various agonists in human arteries in vitro. Human mammary artery rings were obtained during aortocoronary bypass operations. Rings were suspended in organ baths for isometric tension measurements. Concentration response curves induced by serotonin (0.01-30 mumol/l), histamine (0.01-300 mumol/l), and angiotensin II (0.1-100 nmol/l) were generated after pre-incubation for 30 min with either 17 beta-estradiol (3 mumol/l) or solvent (0.2% ethanol). The presence of 17 beta-estradiol significantly reduced the maximal contractile effects induced by histamine, serotonin, and angiotensin II, but not by 80 mmol/l potassium chloride. It is concluded that short-term incubation with 17 beta-estradiol reduces the maximal contractile responses to serotonin, histamine, and angiotensin II. These modulating effects of estrogen on vascular tone may contribute to the proposed beneficial role of estrogen replacement therapy on the incidence of myocardial infarction in postmenopausal women.
 ...
PMID:Contractile responses to histamine, serotonin, and angiotensin II are impaired by 17 beta-estradiol in human internal mammary arteries in vitro. 912 39

In ethanol-fed rats, supplementation of the diet with soybean polyenylphosphatidylcholine (3 g/liter for 21 days) markedly decreased postprandial VLDL-triglycerides and both VLDL- and LDL-cholesterol levels, whereas it maintained high levels of HDL-cholesterol, compared to an equivalent intake of choline and polyunsaturated fatty acids. By contrast, there were no changes in the serum lipoproteins of the pair-fed controls. The prevention of alcoholic hypertriglyceridemia was associated with marked attenuation of the alcoholic fatty liver and it occurred despite a slight increase in fat absorption. Thus, the administration of polyenylphosphatidylcholine not only attenuates the hepatotoxicity of ethanol, but also increases the HDL/LDL cholesterol ratio, which may be beneficial for the prevention of atherosclerosis and coronary heart disease.
 ...
PMID:Polyenylphosphatidylcholine decreases alcoholic hyperlipemia without affecting the alcohol-induced rise of HDL-cholesterol. 936 95

The oxidative modification of low density lipoproteins (LDL) has been implicated in the development of atherosclerosis. This study examined the effect of red wine, ethanol and red wine stripped of phenols on copper-mediated and azo-initiated LDL oxidation. Red wine containing phenolic compounds (0.025-20 mg/l gallic acid equivalents) increased the lag time of conjugated diene formation, inhibited the generation of thiobarbituric acid reactive substances (TBARS) and decreased the relative electrophoretic mobility of LDL in a concentration-dependent manner. These changes were not apparent in LDL incubated with ethanol or red wine stripped of phenols. In other experiments, red wine (75 mg/l gallic acid equivalents) was incubated with plasma at 37 degrees C for 3 h. The LDL isolated from this plasma displayed a 60% increase in lag time following copper-mediated oxidation. Uptake of this LDL by cultured J774 macrophages was three-fold lower than control LDL. Red wine was fractionated into phenolic acids (fraction 1), catechins and monomeric anthocyanidins (fraction 2), flavonols (fraction 3) and polymeric anthocyanidins (fraction 4). All red wine fractions prolonged the time before LDL oxidation. Fraction 2 displayed a significantly greater antioxidant activity than fractions 3 and 4 (but not fraction 1) in at least one pro-oxidant model. In conclusion we have shown that antioxidant compounds in red wine can associate with LDL particles following an incubation in whole plasma, can exert an antioxidant effect and, in so doing, can inhibit the uptake of the lipoprotein by macrophages. This antioxidant effect of red wine was apparent in most of the phenolic fractions separated from wine, particularly catechins, monomeric anthocyanidins and phenolic acids.
Atherosclerosis 1997 Nov
PMID:Red wine and fractionated phenolic compounds prepared from red wine inhibit low density lipoprotein oxidation in vitro. 939 77

Epidemiologic studies suggest that moderate amounts of ethanol may reduce cardiovascular risk. The mechanisms of the alcohol-associated risk reduction are not known exactly. Vascular smooth muscle cell proliferation represents an important phenomenon in the pathogenesis of atherosclerosis. Recently, it was suggested that metabolic changes during the postprandial phase may be important in the pathogenesis of atherosclerosis. Therefore, we evaluated the effect of postprandial plasma with and without ethanol on the proliferation of rat vascular smooth muscle cells. Identical meals containing 1 g fat/kg body wt were given with and without ethanol (38 +/- 0.5 g) to eight healthy young men. Blood was drawn hourly during an 8-h postprandial period; the plasma was separated and added to the cell cultures (0.3%, by vol). The proliferative response (DNA synthesis) of these cells was assessed by measuring the incorporation of [methyl-3H]thymidine. The maximal blood ethanol concentration of 11.5 +/- 0.6 mmol/L (mean +/- SEM) was attained within the first hour. The ingestion of the meal with ethanol led to a 20% reduction in the capacity of postprandial plasma to induce thymidine incorporation into smooth muscle cells compared with the meal without ethanol (P < 0.05). These results suggest that ethanol may reduce cardiovascular risk by modulating vascular muscle cell growth during the postprandial period. Considering the amount of time humans spend in the postprandial state during their lifetimes, these findings may be of great importance in the pathogenesis of atherosclerosis.
 ...
PMID:Ethanol suppresses smooth muscle cell proliferation in the postprandial state: a new antiatherosclerotic mechanism of ethanol? 945 84

Oxidized low density lipoproteins (LDL) are believed to play a central role in the events that initiate atherosclerosis. Antioxidants have been shown to decrease the oxidation of LDL, leading to the diminution of atherosclerosis. Since it is well-known that decreased levels of dehydroepiandrosterone (DHEA) are linked to the development of atherosclerosis, we studied the modulation of the oxidation of LDL by DHEA. LDL were obtained from 10 healthy subjects and oxidized by free radicals produced by gamma-radiolysis of ethanol-water mixtures. The formation of conjugated dienes and thiobarbituric acid-reactive substances (TBARS), the vitamin E content, as well as the incorporation of 4-[14C]DHEA in LDL and the chemotactic effect of oxidized LDL in the presence of DHEA towards monocytes, were investigated. It was found that DHEA was able to inhibit the oxidation of LDL by reducing over 90% of the conjugated dienes and TBARS formation, as well as by reducing the vitamin E disappearance and significantly decreasing the chemotactic activity towards monocytes. Our results suggest that DHEA exerts its antioxidative effect by protecting the endogenous vitamin E of LDL.
Atherosclerosis 1998 Jan
PMID:Dehydroepiandrosterone protects low density lipoproteins against peroxidation by free radicals produced by gamma-radiolysis of ethanol-water mixtures. 954 36

Stroke (cerebrovascular accident, CVA) is the third leading cause of death and an important cause of hospital admission and long term disability in Australia. Atherosclerotic lesions at the bifurcation of the common carotid artery are the most common cause of stroke. On occasion these lesions are partially calcified and visible on a conventional panoramic dental radiograph. The atheroma may appear either as a nodular radiopaque mass or as two radiopaque vertical lines within the soft tissues of the neck at the level of the lower margin of the third cervical vertebra (C3). These opacities are separate and distinct from the hyoid bone and variably appear above or below it. Dentists should scrupulously review the panoramic radiographs of all individuals over age 55 with medical histories of hypertension, diabetes mellitus, hypercholesteraemia and coronary artery disease, or whose behaviour includes smoking, ethanol abuse, or dietary indiscretion coupled with overweight and a sedentary lifestyle which are known to be associated with atherosclerosis and stroke.
 ...
PMID:Identification of stroke prone patients by panoramic radiography. 958 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>