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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ergocalciferol (320,000 or 480,000 IU/kg) plus cholesterol (60 mg/kg) in olive oil solution was administered daily on 1, 2, or 4 consecutive days to pregnant rats from 9,10, 14, or 18 of gestation. The control animals received only olive oil. Disseminated lesions of metastic calcinosis were found in various tissues, in the coronary arteries and myocardium, in the media of the abnormal aorta, in the lung and pleura, in the gastoinstestinal tract, and in the kidney. This is in contrast to the atherosclerosis described in nonpregnant rats fed a similiar diet. A significant decline in maternal weight as well as a high rate of morbidity and mortality was observed. In mothers killed on day 22 of pregnancy, fetal and placental growths appeared significantly retarded suggesting a direct effect of the steroid or its more active metabolite, 1,25-dihydroxycholecalciferol, on the fetus or the trophoblastic tissue. Fetal bone lesionsassociated with a generalized retardation of ossification, placental edema, or calcification accompanied by a loss of the normal structure of the placenta and degenerative manifestation at this level were observed. Moreover, we noted a striking alteration of the fetal face in 33-39% of experimental fetuses, called by us carnival fetuses.
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PMID:Effects of massive doses of ergocalciferol plus cholesterol on pregnant rats and their offspring. 107 62

To understand further the antiatherogenic mechanism of probucol, the antioxidant effect of this agent was studied on specific cholesterol oxidation products in plasma and aortic wall in equally hypercholesterolemic New Zealand white rabbits. In order to maintain equal plasma total cholesterol levels, five control rabbits (C group) received a 1% followed by a 0.5% cholesterol enriched diet, while the probucol treated rabbits (C+P group) received a graded increase in the cholesterol supplemented diet from 1% to 3%; probucol supplementation was constant at 1%. After 9 weeks of feeding, the plasma oxysterols, cholest-5-ene-3 beta,7 alpha-diol, cholest-5-ene-3 beta,7 beta-diol, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol and 5 alpha-cholestane-3 beta,5,6 beta-triol significantly increased over baseline levels in both experimental groups. However, the increase in all these products in plasma was 20-60% less in the C+P group than the C group (P < 0.05). Furthermore, the C+P aortic wall cholesterol oxide concentrations were 50-90% less than the C group (P < 0.05). The oxysterol pattern of the aortic wall was similar to plasma. Additionally, the aortic wall cholesterol content in the C+P group was 50% less than the C group (P < 0.05). The plasma cholesterol levels were not significantly different at any time point during the study and the cholesterol oxide content in the diets was the same. These results are consistent with the contention that the antioxidant properties of probucol serve as the basis for its antiatherogenic effects in vivo.
Atherosclerosis 1992 Oct
PMID:Probucol reduces plasma and aortic wall oxysterol levels in cholesterol fed rabbits independently of its plasma cholesterol lowering effect. 146 46

To determine the relationship between plasma and arterial wall oxysterols, plasma and aortic tissue from 7 New Zealand White rabbits fed a high cholesterol (1%) diet for 6 weeks was compared to plasma and aortic tissue from 7 normocholesterolemic rabbits fed standard rabbit chow. Cholesterol and cholesterol oxide fractions were isolated and analyzed by gas chromatography. Normocholesterolemic plasma and aortic tissue contained low levels of cholest-5-ene-3 beta, 7 alpha-diol, cholesta-3,5-dien-7-one, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol, cholest-5-ene-3 beta, 7 beta-diol, and 5 alpha-cholestane-3 beta, 5,6 beta-triol while hypercholesterolemic plasma and atherosclerotic aorta contained significantly higher levels (P less than 0.05) of these products. Furthermore, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol not found in normocholesterolemic plasma or aortic tissue was present in substantial amounts in both hypercholesterolemic plasma and atherosclerotic aortic tissue. Cholest-5-ene-3 beta,25-diol and 3 beta-hydroxycholest-5-ene-7- one not present in normocholesterolemic aorta were present in the atherosclerotic aorta. The oxysterol chromatographic patterns of normocholesterolemic plasma and normocholesterolemic aortic tissue were similar to each other as were the oxysterol chromatographic patterns of hypercholesterolemic plasma and atherosclerotic aortic tissue. The chromatographic patterns between the normocholesterolemic and hypercholesterolemic samples differed however. Possible absorption of the low levels of cholesterol oxides present in the cholesterol feed could account for the elevation of only some of the oxysterols. We conclude that cholesterol oxides exist at some basal level in normocholesterolemia and that these levels are increased by cholesterol-feeding which results in hypercholesterolemia. Our findings demonstrate that there is a strong relationship between plasma and aortic arterial wall levels of cholesterol oxides and suggest that in addition to exogenous sources, formation of cholesterol oxides proceeds via free radical oxidation acting upon elevated cholesterol levels resulting in the accumulation of these potentially cytotoxic and atherogenic products.
Atherosclerosis 1991 Aug
PMID:Cholesterol feeding increases plasma and aortic tissue cholesterol oxide levels in parallel: further evidence for the role of cholesterol oxidation in atherosclerosis. 179 39

Mammalian cell membranes are much more sensitive to changes in serum ion concentrations than they are to serum cholesterol. Because of this, arterial cells function normally only in a very narrow range of serum ion concentrations. Unfortunately, new introductions into the food supply have been made in the diet since 1920 which may perturb the delicate relationships between arterial cell membranes and the blood serum to which they are exposed. For example, powerful surface active agents are used to emulsify fats in a host of popular food items. None of them have been adequately tested for their possible role in changing phospholipid head group composition of arterial or myocardial cell membranes. Ocean salt has been replaced by refined table salt removing a rich source of magnesium from the diet of Northern Europeans and Americans. Excessive amounts of Vitamin D, which may calcify soft tissue, have been added to the diet as a means of preventing a disease that does not develop in babies exposed to sunshine. The introduction of hydrogenated vegetable oil to the diet has helped to stimulate per capita fat consumption to almost twice the level of 1920. How the introduction of such technology has changed arterial cell membrane structure or function has not been considered. It is now possible to consider the influence of this technology on the food supply by the application of modern genetic engineering methods. The application of this type of methodology in the study of cholesterol metabolism and its role in atherosclerosis may help to find means of preventing heart disease and strokes.
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PMID:Serum factors which alter cell membranes. 331 Oct 13

Sitostanol (24-ethyl-5 alpha-cholestan-3 beta-ol), a hydrogenated derivative of sitosterol, was administered in a low dose (1.5 g/day) for 4 weeks to 6 patients with hypercholesterolemia. Total cholesterol was reduced significantly after 3 and 4 weeks by 10 and 15%, respectively. The reduction of total cholesterol was entirely due to a fall in LDL cholesterol. Total triglycerides and HDL cholesterol were not altered. Two weeks after cessation of sitostanol administration serum cholesterol returned to pretreatment levels. No significant amounts of sitostanol could be detected in plasma during therapy. These results suggest that low-dose sitostanol might be a useful hypolipidemic agent for the treatment of mild hypercholesterolemia.
Atherosclerosis 1986 Sep
PMID:Effect of low-dose sitostanol on serum cholesterol in patients with hypercholesterolemia. 376 90

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one has been found to have significant hypocholesterolemic activity upon oral administration at a daily dosage of 75 mg/kg of body weight to Rhesus monkeys fed a diet of moderate cholesterol (Chol) content [0.19 mg/kcal (1 cal = 4.184 J) of diet]. The reductions in total serum Chol levels (mean, -41%) were associated with even more striking reductions (mean, -61%) in the levels of low density lipoprotein (LDL) plus very low density lipoprotein (VLDL) Chol and also with increases in high density lipoprotein (HDL) Chol levels (mean, +61%). The mean increase in HDL Chol was 33 mg/dl. In one animal, that with the lowest pretreatment HDL Chol level, the extent of the rise was 49 mg/dl (+120%). These changes were associated with reductions in the % of total serum Chol associated with LDL/VLDL, in the ratios of total Chol to HDL Chol and of LDL/VLDL Chol to HDL Chol, and in the levels of LDL protein. The 15-ketosterol also increased the % of total Chol associated with HDL, increased the level of HDL protein, and induced a shift in the HDL profile to one in which the HDL2 species was the predominant species. All of these changes are those generally considered desirable for the treatment and/or prevention of atherosclerosis.
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PMID:5 alpha-Cholest-8(14)-en-3 beta-ol-15-one lowers serum cholesterol and induces profound changes in the levels of lipoprotein cholesterol and apoproteins in monkeys fed a diet of moderate cholesterol content. 659 30

Phytosterolaemia (sitosterolaemia) is a very rare inherited sterol storage disease characterized by tendon and tuberous xanthomas and by a predisposition to atherosclerosis. We here describe the first Scandinavian case. The 14-year-old female patient was found to have markedly elevated circulating levels of plant sterols (sitosterol, sitostanol, campesterol, stigmasterol), and the levels of these sterols were 20-50 times higher than in her healthy sister and heterozygous parents. In addition to the usual serum plant sterols we found a new major sterol in the patient tentatively identified as episterol or fecosterol (24-methyliden-cholest-7 (or 8)-en-3 beta-ol). A newly developed method based on the use of deuterium labelled cholesterol and plant sterols was used to measure sterol absorption in the patient and her relatives. Absorption of sitosterol averaged 20% in the patient and ranged from 4 to 8% in the relatives. Absorption of campesterol averaged 31% in the patient and ranged from 15 to 18% in her relatives. Absorption of cholesterol averaged 63% in the patient and ranged from 35 to 45% in the relatives. Cholesterol synthesis appeared to be reduced in the patient and was 46-52% of that of her relatives.
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PMID:Phytosterolaemia in a Norwegian family: diagnosis and characterization of the first Scandinavian case. 876 27

We have shown earlier that sitostanol ester margarine lowers serum cholesterol by inhibiting cholesterol absorption so that, theoretically, there could be interference with the absorption of fat-soluble vitamins. Accordingly, we investigated whether sitostanol ester margarine affects the serum levels of vitamin D, retinol, alpha-tocopherol and alpha- and beta-carotenes during 1-year treatment in 102 subjects and 49 controls with moderate hypercholesterolemia. The vitamins were assayed at baseline on home diet, on margarine alone, after 1 year's consumption of sitostanol ester margarine and after an additional 2 months on home diet. In the sitostanol group, serum plant sterols, indicators of cholesterol absorption efficiency, were reduced up to -38% in relation to controls from home diet (P < 0.01) indicating that cholesterol absorption was markedly reduced. Vitamin D and retinol concentrations and the ratio of alpha-tocopherol to cholesterol were unchanged by sitostanol ester. Serum beta-carotenes and alpha-carotene concentration but not proportion were reduced in the sitostanol group from baseline and in relation to controls (P < 0.01). Retinol and vitamin D were unassociated with serum cholesterol, plant sterols or other vitamins, whereas alpha-tocopherol and carotenes were significantly associated with serum plant sterols suggesting that the higher cholesterol absorption efficiency, the higher the alpha-tocopherol and carotene levels in serum. We conclude that sitostanol ester did not affect vitamin D and retinol concentrations and alpha-tocopherol/cholesterol proportion, but reduced serum beta-carotene levels. Alpha-tocopherol and carotenes, but not vitamin D and retinol, were related to serum cholesterol and cholesterol absorption.
Atherosclerosis 1999 Aug
PMID:Retinol, vitamin D, carotenes and alpha-tocopherol in serum of a moderately hypercholesterolemic population consuming sitostanol ester margarine. 1048 54

Cardiovascular diseases are the leading causes of mortality among patients with end-stage renal disease (ESRD), with arterial disease and left ventricular hypertrophy being the two principal factors of the high mortality rate in this population. In addition to traditional risk factors (age, gender, diabetes, hypertension, lifestyle, hyperlipidemia, smoking, hyperhomocystinemia), inflammation, oxidative stress and disorders of mineral metabolism may contribute to cardiovascular risk in patients with uremic syndrome. High serum phosphate may influence vascular calcifications directly and indirectly, by worsening secondary hyperparathyroidism. Several treatment options are available for the treatment of hyperphosphatemia and secondary hyperparathyroidism in patients with ESRD. The treatment approach includes a diet low in phosphorus, with less than 1 g/kg/day of protein. Vitamin D supplementation is an important part of treatment. Phosphate binding agents are in most of the patients necessary in addition to diet. Aluminum hydroxide has been widely used for many years. It is very potent, but also very toxic, with severe encephalopathy as the most dangerous side effect. Calcium salts are less potent, and were considered safe for use in patients on dialysis. However, improvement in the understanding of vascular calcifications has demonstrated that calcium overload significantly contributes to widespread atherosclerosis in patients with ESRD. Sevelamer-hydrochloride is a novel non-aluminum, non-calcium containing phosphate binder, which is capable of reducing the levels of phosphorus as well as of low-density lipoprotein cholesterol, and increasing high-density lipoprotein cholesterol.
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PMID:[Hyperphosphatemia and cardiovascular risk in patients on dialysis]. 1550 84

Vitamin D analogs provide survival benefit for chronic kidney disease patients with cardiovascular complications. Activation of smooth muscle cells plays a role in cardiovascular diseases. It is not known how Vitamin D analogs modulate gene expression in smooth muscle cells. In this study, DNA microarray technology was used to assess the gene expression profile in human coronary artery smooth muscle cells treated with 0.1microM 1alpha,25-dihydroxyvitamin D3 (calcitriol) or paricalcitol (an analog of calcitriol) for 30 h. The effects of calcitriol and paricalcitol were similar. A total of 176 target genes were identified with 115 up-regulated and 61 down-regulated genes in the paricalcitol group. Target genes fall into various categories including cell differentiation/proliferation. Real-time RT-PCR analysis demonstrated that paricalcitol dose- and time-dependently regulated the expression of IGF1, WT1 and TGFbeta3, three genes known to modulate cell proliferation. Paricalcitol also down-regulated the expression of natriuretic peptide precursor B and thrombospondin 1. Both drugs inhibited cell proliferation in a dose-dependent manner. This study identified genes not previously known to be regulated by VDR, providing insight into understanding the role of VDR on regulating smooth muscle cell growth, thrombogenicity, fibrinolysis and endothelial regeneration.
Atherosclerosis 2006 May
PMID:Effects of Vitamin D analogs on gene expression profiling in human coronary artery smooth muscle cells. 1609 99


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