cytellin and Arteriosclerosis

Topics: Arteriosclerosis; Cholestyramine Resin; Contraindications; Diagnosis, Differential; Genes, Recessive; Humans; Ion Exchange Resins; Lipid Metabolism, Inborn Errors; Phytosterols; Prognosis; Sitosterols; Xanthomatosis

Although plant sterols (phytosterols) and cholesterol have similar chemical structures, they differ markedly in their synthesis, intestinal absorption, and metabolic fate. Phytosterols inhibit intestinal cholesterol absorption, thereby lowering plasma total and low-density lipoprotein (LDL) cholesterol levels. In 16 recently published human studies that used phytosterols to reduce plasma cholesterol levels in a total of 590 subjects, phytosterol therapy was accompanied by an average 10% reduction in total cholesterol and 13% reduction in LDL cholesterol levels. Phytosterols may also affect other aspects of cholesterol metabolism that contribute to their antiatherogenic properties, and may interfere with steroid hormone synthesis. The clinical and biochemical features of hereditary sitosterolemia, as well as its treatment, are reviewed, and the effects of cholestyramine treatment in 12 sitosterolemic subjects are summarized. Finally, new ideas for future research into the role of phytosterols in health and disease are discussed.

Topics: Anticholesteremic Agents; Arteriosclerosis; Cholesterol; Cholestyramine Resin; Humans; Intestinal Absorption; Phytosterols; Sitosterols

Topics: Arteriosclerosis; Child; Cholelithiasis; Cholestyramine Resin; Clofibrate; Colestipol; Dextrothyroxine; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins, LDL; Lipoproteins, VLDL; Nicotinic Acids; Phenoxyacetates; Sitosterols

Topics: Alcoholism; Arteriosclerosis; Blood Circulation; Carbon Monoxide; Cholestyramine Resin; Diabetes Mellitus; Humans; Hyperlipidemias; Hypertension; Nicotinic Acids; Physical Education and Training; Risk; Sitosterols; Smoking

Sitosterolemia is a recessively inherited disorder that results from mutations in either ABCG5 or G8 proteins, with hyperabsorption of dietary sterols and decreased hepatic excretion of plant sterols and cholesterol. As a consequence of markedly elevated plasma and tissue sitosterol and campesterol levels, premature atherosclerosis develops.. In this multicenter, double-blind, randomized, placebo-controlled study, we examined whether treatment with ezetimibe, an inhibitor of cholesterol absorption, reduces plant sterol levels in patients with sitosterolemia. After a 3-week placebo run-in, 37 patients were randomized to receive placebo (n=7) or ezetimibe 10 mg/d (n=30) for 8 weeks. Sitosterol concentrations decreased by 21% (P<0.001) in patients treated with ezetimibe compared with a nonsignificant 4% rise in those on placebo (between-group P<0.001). The reduction in sitosterol from baseline was progressive, with further decline observed at each subsequent biweekly visit. Campesterol also progressively declined, with a mean decrease after 8 weeks of 24% with ezetimibe and a mean increase of 3% with placebo treatment (between-group P<0.001). Reductions in plant sterol concentrations were similar irrespective of whether patients were undergoing concomitant treatment with resin or statin. Reductions in total sterols and apolipoprotein B were also observed. Ezetimibe was well tolerated, with no serious treatment-related adverse events or discontinuations due to adverse events being reported.. Ezetimibe produced significant and progressive reductions in plasma plant sterol concentrations in patients with sitosterolemia, consistent with the hypothesis that ezetimibe inhibits the intestinal absorption of plant sterols as well as cholesterol, leading to reductions in plasma concentrations.

Topics: Adolescent; Adult; Aged; Anticholesteremic Agents; Apolipoproteins B; Arteriosclerosis; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Azetidines; Child; Cholesterol; Cholesterol, Dietary; Double-Blind Method; Ezetimibe; Female; Genes, Recessive; Humans; Intestinal Absorption; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Phytosterols; Sitosterols; Treatment Outcome

Treatment with carbamazepine (CBZ) affects cholesterol concentrations, but little is known about the precise nature and underlying mechanisms of changes in lipoprotein metabolism. We investigated prospectively the effects of CBZ on lipid metabolism in normolipemic adults. In 21 healthy males, lipoprotein and noncholesterol sterol concentrations were measured before and during treatment with CBZ for 70 +/- 18 days. Thirteen subjects underwent kinetic studies of apolipoprotein-B (ApoB) metabolism with the use of endogenous stable isotope labeling. Lipoprotein kinetic parameters were calculated by multicompartmental modeling. Significant increases in total cholesterol, in ApoB-containing lipoproteins [very-low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low-density lipoprotein (LDL)], and in triglycerides, but not in high-density lipoprotein (HDL), were observed. Lipoprotein particle composition remained unchanged. Mean fractional catabolic and production rates of ApoB-containing lipoproteins were not significantly different, although mean production rates of VLDL and IDL were substantially increased (+46 +/- 139% and +30 +/- 97%, respectively), whereas mean production of LDL remained unchanged (+2.1 +/- 45.6%). Cholestanol in serum increased significantly but not the concentrations of plant sterols (campesterol, sitosterol) and the cholesterol precursors (lathosterol, mevalonic acid). There was a significant correlation between the decrease in free thyroxine and the increase in IDL cholesterol. Treatment with CBZ increases mainly ApoB-containing lipoproteins. CBZ seems not to influence endogenous cholesterol synthesis or intestinal absorption directly. The increase is neither related to increased ApoB production nor to decreased catabolism but is rather due to changes in the conversion cascade of IDL particles, most likely as an indirect effect through a decrease in thyroid hormones.

Topics: Adult; Anticonvulsants; Arteriosclerosis; Body Composition; Body Weight; Carbamazepine; Cholestanol; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Diet; Humans; Hydrocortisone; Intestinal Absorption; Lipoproteins; Male; Mevalonic Acid; Phytosterols; Sitosterols

Plant sterol supplementation reduces serum cholesterol concentration but may increase serum plant sterol concentrations, especially in children. We determined whether natural dietary plant sterols derived mainly from vegetable oil or margarine in early childhood affect serum concentrations of plant sterols (campesterol and sitosterol) and cholesterol precursor sterols (Delta-8 cholestenol, desmosterol, and lathosterol), reflecting endogenous cholesterol synthesis. We measured the serum sterol concentrations using gas liquid chromatography in 20 healthy 13-mo-old intervention children in a randomized, prospective study designed to decrease exposure of the children to known environmental atherosclerosis risk factors and in 20 control children. The diet of the intervention children was rich in plant sterols due to replacement of milk fat with vegetable fat, whereas the diet of the control children contained only small amounts of plant sterols. The intervention children consumed twice as much plant sterols as the control children (P < 0.001). Their serum concentrations of campesterol and sitosterol were 75% and 44% higher, respectively, than those in the control children (P < 0.001 for both), but serum cholesterol precursor sterol concentrations did not differ between the two groups. We conclude that doubling dietary plant sterol intake almost doubles serum plant sterol concentrations in 13-mo-old children, but has no effect on endogenous cholesterol synthesis. Relative intestinal absorption of natural plant sterols from the diet in early childhood is similar to that in adults.

Topics: Arteriosclerosis; Case-Control Studies; Cholesterol; Chromatography, Gas; Desmosterol; Diet Records; Female; Humans; Hypolipidemic Agents; Infant; Intestinal Absorption; Male; Margarine; Phytosterols; Plant Oils; Prospective Studies; Risk Factors; Sitosterols

Topics: Absorption; Animals; Arteriosclerosis; Cholesterol; Cholesterol, Dietary; Cholestyramine Resin; Clinical Trials as Topic; Food; Humans; Hypercholesterolemia; Phytosterols; Risk; Sitosterols

Phytosterol oxidation products (oxyphytosterols) are formed during the processing and storage of foods. However, it is unknown whether oxyphytosterols affect human health. To address these issues, we prepared beta-sitosterol and campesterol oxides, evaluated their lymphatic absorption in rats, and examined the effect of an oxyphytosterol diet on atherosclerosis in apolipoprotein (apo) E-deficient mice. The lymphatic absorption of cholesterol and 6 oxyphytosterols (7alpha-hydroxy, 7beta-hydroxy, beta-epoxy, alpha-epoxy, dihydroxy, and 7-keto) of beta-sitosterol or campesterol was assessed in thoracic duct-cannulated rats fed an AIN-93G-based diet containing 2.5 g of cholesterol, oxyphytosterols, or intact phytosterols per kg. Lymphatic recoveries (on a mass basis) of oxycampesterols (15.9 +/- 2.8%, n = 10) and oxysitosterols (9.12 +/- 1.77%, n = 10) were higher than for campesterol (5.47 +/- 1.02%, n = 12, P < 0.05) and beta-sitosterol (2.16 +/- 0.37%, n = 12, P < 0.05), but lower than for cholesterol (37.3 +/- 8.3%, n = 6, P < 0.05). Apo E-deficient mice were fed an AIN-93G-based diet containing 0.2 g oxyphytosterols or intact phytosterols per kg for 9 wk. Diet-derived oxyphytosterols accumulated in the serum, liver, and aorta. Furthermore, the oxyphytosterol diet increased oxycholesterol in the serum compared to the phytosterol diet. However, there was no significant difference between the 2 groups in the serum and aortic cholesterol concentration, the lesion area in the aortic root, or 8-iso-prostaglandin F2alpha concentration in the urine. These results indicate that exogenous oxyphytosterols are well-absorbed and accumulate in the body, but do not promote the development of atherosclerosis in apo E-deficient mice.

Topics: Animals; Apolipoproteins E; Arteriosclerosis; Cholesterol; Intestinal Absorption; Lymphatic System; Male; Mice; Oxidation-Reduction; Phytosterols; Rats; Rats, Sprague-Dawley; Sitosterols; Tissue Distribution

Sitosterolaemia (phytosterolaemia) is an autosomal recessive disorder characterised by the presence of tendon xanthomas in the face of normal or mildly elevated plasma cholesterol levels, premature atherosclerotic disease and has diagnostically elevated plasma and tissue plant sterol concentrations. Affected individuals show an increased absorption of both cholesterol and sitosterol from the diet, decreased bile clearance of these sterols and their metabolites resulting in markedly expanded whole body cholesterol and sitosterol pools. The defective gene is therefore hypothesised to play a crucial role in regulating dietary cholesterol absorption, and its elucidation may shed light on these molecular processes. We have previously localised the defective gene to human chromosome 2p21, between microsatellite markers D2S1788 and D2S1352, a distance of approximately 15 cM. Recently, the disease locus interval has been narrowed to lie between D2S2294 and D2S2291/D2S2174. We have constructed a high-resolution YAC and BAC contigs by using known STSs and generating novel STSs from the minimal interval. Eight previously identified genes and 60 ESTs were mapped to these contigs. The BAC contig contains 60 BAC clones and 108 STSs and encompasses a physical distance of approximately 2.0 cM between microsatellite markers D2S2294 and D2S2291. These results will not only facilitate cloning of the sitosterolaemia gene, but also other disease genes located in this region, and accelerate sequencing of the corresponding genomic clones.

Topics: Arteriosclerosis; Chromosome Mapping; Chromosomes, Artificial, Bacterial; Chromosomes, Artificial, Yeast; Chromosomes, Human, Pair 2; Cloning, Molecular; Contig Mapping; Databases, Factual; DNA Primers; Expressed Sequence Tags; Humans; Metabolic Diseases; Physical Chromosome Mapping; Polymerase Chain Reaction; Sitosterols; Transcription, Genetic

Sitosterolaemia (also known as phytosterolaemia, MIM 210250) is a rare recessive autosomal inherited disorder, characterised by the presence of tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. The defective gene is hypothesised to play an important role in regulating dietary sterol absorption and biliary secretion, thus defining a molecular mechanism whereby this physiological process is carried out. The disease locus was localised previously to chromosome 2p21, in a 15 cM interval between microsatellite markers D2S1788 and D2S1352 (based upon 10 families, maximum lodscore 4.49). In this study, we have extended these studies to include 30 families assembled from around the world. A maximum multipoint lodscore of 11.49 was obtained for marker D2S2998. Homozygosity and haplotype sharing was identified in probands from non-consanguineous marriages from a number of families, strongly supporting the existence of a founder effect among various populations. Additionally, based upon both genealogies, as well as genotyping, two Amish/Mennonite families, that were previously thought not to be related, appear to indicate a founder effect in this population as well. Using both homozygosity mapping, as well as informative recombination events, the sitosterolaemia gene is located at a region defined by markers D2S2294 and Afm210xe9, a distance of less than 2 cM.

Topics: Arteriosclerosis; Cholesterol, Dietary; Chromosome Mapping; Chromosomes, Human, Pair 2; Diet; Founder Effect; Genotype; Haplotypes; Homozygote; Humans; Intestinal Absorption; Linkage Disequilibrium; Metabolic Diseases; Microsatellite Repeats; Models, Genetic; Pedigree; Phylogeny; Sitosterols

The hypolipidemic and anti-atherosclerotic effects of vegetable oil- and wood-based dietary plant stanol esters were compared in female apoE*3-Leiden transgenic mice at relevant plasma cholesterol levels. The plant stanol esters derived from vegetable oil (sitostanol 65.7%, campestanol 30.1%) had different contents of sitostanol and campestanol than the plant stanol esters derived from wood (sitostanol 87.6%, campestanol 9.5%) or from a mixture of vegetable oil and wood (sitostanol 73.0%, campestanol 24.7%). The mice (10 per group) received for 38 weeks a control diet or diets containing 1.0% (w/w) plant stanol esters derived from either vegetable oil, wood or a mixture of both. Vegetable oil (-46%), wood (-42%) and vegetable oil/wood (-51%) plant stanol esters decreased the plasma cholesterol levels (P<0.0001) by reducing the cholesterol content in plasma very low density-, intermediate density- and to a lesser extent in low density-lipoprotein. Plant stanol ester feeding did not change plasma triglyceride levels. Dietary plant stanol esters reduced the atherosclerotic lesion area by 91+/-13% (vegetable oil), 97+/-4% (wood) and 78+/-34% (vegetable oil/wood) (P<0.0001) and the severity from regular intimal fatty streaks/mild plaques (on average type 2--3 lesions) in controls to individual intimal foam cells (

Topics: Animals; Apolipoprotein E3; Apolipoproteins E; Arteriosclerosis; Cholesterol; Dietary Fats, Unsaturated; Female; Mice; Mice, Transgenic; Mutation; Plant Oils; Severity of Illness Index; Sitosterols; Triglycerides; Wood

Sitosterolemia is a rare, recessively inherited disease characterized clinically by accelerated atherosclerosis and xanthomas and biochemically by hyperabsorption and retention of sitosterol and other plant sterols in tissues. Decreased cholesterol biosynthesis and inhibition of 3-hydroxy-3-methylgluratyl coenzyme A (HMG-CoA) reductase and other enzymes in the biosynthetic pathway have been associated with enhanced low-density lipoprotein (LDL) receptor function. We examined the effects of cholesterol and sitosterol on sterol concentrations and composition and HMG-CoA reductase activity in monocyte-derived macrophages (MDM) from 12 control and 3 homozygous sitosterolemic subjects. The cells were cultured up to 7 days in media devoid of plant sterols, but containing increasing amounts of serum cholesterol. Before culture, MDM from the homozygous sitosterolemic subjects contained 22% more total sterols than cells from control subjects. Plant sterols and stanols represented 15.6% of MDM total sterols in sitosterolemic cells, but only 3.8% in control cells. After 7 days of culture in 10% delipidated serum (DLS) (20 microg/mL cholesterol, no sitosterol), all plant sterols were eliminated so that cells from both phenotypes contained only cholesterol. When DLS was replaced with fetal bovine serum (FBS) (300 micromL cholesterol), with and without addition of 200 microg/mL LDL, cholesterol levels in MDM from sitosterolemic subjects increased 108% (P <.05) compared with a 65% increase (P <.04) in control MDM cultured similarly. MDM HMG-CoA reductase activity from the 3 sitosterolemic subjects, which was significantly lower than controls at baseline (24 +/- 3 v 60 +/- 10 pmol/mg/min, P <.05), was not downregulated by increased cellular cholesterol levels, as observed in control cells. Control MDM were also cultured in medium that contained 10% DLS and was supplemented with 100 microg/mL cholesterol or sitosterol dissolved in ethanol or the ethanol vehicle alone. In contrast to cellular cholesterol accumulation, which significantly downregulated HMG-CoA reductase activity (-53%, P <.05), the increase in cellular sitosterol up to 25.1% of total sterols did not change MDM HMG-CoA reductase activity. Evidence of a normal HMG-CoA reductase protein in sitosterolemic cells, which was not derepressed upon removal of cellular sitosterol, and the failure of cellular sitosterol to inhibit normal HMG-CoA reductase activity argue against feedback inhibition by sitosterol as a me

Topics: Adult; Arteriosclerosis; Cells, Cultured; Cholesterol; Culture Media; Enzyme Activation; Female; Humans; Hydroxymethylglutaryl CoA Reductases; Macrophages; Male; Middle Aged; Sitosterols

Topics: Adult; Arteriosclerosis; Cholesterol, Dietary; Female; Humans; Male; Sitosterols

Sitosterolemia is an inherited recessive disease characterized by abnormally increased plasma and tissue plant sterol concentrations. Patients hyperabsorb sitosterol. In addition, hepatic, ileal, and mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-controlling enzyme in the cholesterol biosynthetic pathway, is markedly suppressed in this disease. It is still controversial whether the down-regulation is due to accumulated sitosterol, but the effect of sitosterol on HMG-CoA reductase activity has not been studied in sitosterolemic tissues. To investigate whether sitosterol inhibits HMG-CoA reductase activity in sitosterolemia, we measured the enzyme activities in liver and cultured skin flbroblasts from patients. Hepatic HMG-CoA reductase activities in patients were decreased 76% (P < .05) as compared with results in control subjects. In contrast, HMG-CoA reductase activities in sitosterolemic fibroblasts were not decreased as compared with results in control fibroblasts, and the activities in all cells were up-regulated similarly when they were exposed to delipidated medium. Because the cultured sitosterolemic fibroblasts contained only trace amounts of plant sterols, we added 20 microg/mL sitosterol directly to the cell medium. Raising the intracellular sitosterol concentration to 7% of cellular cholesterol level increased HMG-CoA reductase activity 23% (P < .05), while the addition of the same amount of cholesterol to the cells reduced the activity 46% (P < .05). Thus, when sitosterolemic skin fibroblasts were used, it was possible to distinguish between the effects of cholesterol and those of sitosterol on the activity of HMG-CoA reductase. These results suggest that reduced HMG-CoA reductase activity in this disease is caused by secondary effects of unknown regulator(s) other than sitosterol.

Topics: Adolescent; Adult; Aorta, Thoracic; Arteriosclerosis; Cells, Cultured; Cholesterol; Female; Fibroblasts; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipid Metabolism, Inborn Errors; Male; Reference Values; Sitosterols

The effects of graded amounts of dietary sitostanol (0.01, 0.2 and 0.8% (w/w)) were examined on plasma lipid-profile, coronary artery plaque development and lecithin:cholesterol acyl transferase activity in male New Zealand White rabbits given semi-purified diets for 10 weeks. All diets provided < 10% energy in the form of fat and contained 0.5% (w/w) cholesterol (C). Rabbits fed the semi-purified diet with 0.8% (w/w) (0.64 g/day) sitostanol had lower plasma total cholesterol (TC) (p = 0.006) (15.2 +/- 4.80 mmol/l) and very low-density lipoprotein-cholesterol (VLDL-C) (p = 0.007) (6.31 +/- 3.11 mmol/l) levels compared to the atherogenic control group (n = 6) (29.6 +/- 5.52 and 17.16 +/- 7.43 mmol/l, respectively). Dietary sitostanol at 0.8% (w/w) depressed plaque accretion in coronary arteries (p = 0.0014) and ascending aorta (p = 0.0004) compared with the atherogenic control, 0.01 and 0.2% (w/w) sitostanol-fed groups. No differences (p = 0.24) in the activity of lecithin:cholesterol acyl transferase (LCAT) were observed across groups, although plasma cholesterol fractional esterification rate was higher (p = 0.004) in the 0.8% (w/w) sitostanol fed animals compared with the atherogenic control. Significant negative correlations were demonstrated between sitostanol intake and plasma TC, LDL-C and VLDL-C levels. Hepatic campesterol levels were correlated (r = 0.3, p = 0.03) with plasma but not hepatic TC concentrations. These results demonstrate that dietary sitostanol at a concentration of 0.8% (w/w) or 0.64 g/day lowered plasma cholesterol levels and depressed atherosclerosis development in rabbits, but did not alter LCAT activity.

Topics: Animals; Anticholesteremic Agents; Arteriosclerosis; Cholesterol; Coronary Vessels; Diet; Esterification; Male; Phosphatidylcholine-Sterol O-Acyltransferase; Phytosterols; Rabbits; Sitosterols

In this report, an 11-year-old boy with diffuse tendinous and tuberous xanthomatosis and a plasma sterol concentration of 555 mg/dL, consisting primarily of cholesterol, is described. Three months after changing from an unrestricted diet to a cholesterol-lowering diet, his plasma sterol concentration decreased to 221 mg/dL. Because of the degree and rapidity of his response to diet, sitosterolemia was suspected. According to results of capillary gas-liquid chromatography of his plasma sterols, there was a sitosterol concentration of 31.3 mg/dL (normal less than 1.0 mg/dL), establishing the diagnosis of sitosterolemia. Addition of cholestyramine therapy (8 g/d) to a low sterol diet further lowered his plasma sterol concentration to 173 mg/dL and led to complete regression of all tuberous xanthomata. Tendinous xanthomata regressed at a slower rate. These findings show that the diagnosis of sitosterolemia should be suspected in severely hypercholesterolemic children (total cholesterol greater than 400 mg/dL) whose plasma cholesterol level is highly responsive to dietary manipulation. The rapid and sustained lowering of plasma cholesterol and regression of xanthomata after treatment with diet and cholestyramine suggest that sitosterolemia is a treatable cause of premature atherosclerosis.

Topics: Arteriosclerosis; Child; Cholestyramine Resin; Combined Modality Therapy; Humans; Hypercholesterolemia; Lipid Metabolism, Inborn Errors; Male; Sitosterols; Xanthomatosis

We measured the turnover and absorption of sitosterol and cholesterol, along with plasma sterol and lipoprotein concentrations, in one control and two subjects with sitosterolemia with xanthomatosis. All individuals consumed the same diet which contained approximately 500 mg/day of cholesterol and 250 mg/day of sitosterol. Sterol absorption was measured by the plasma dual-isotope ratio method and turnover by plasma isotope-kinetic analysis. In two sitosterolemic subjects, 28% and 63% of the sitosterol and 69% and 49% of the cholesterol were absorbed, respectively, compared to 4% of the sitosterol and 44% of the cholesterol in the control. As expected, plasma sitosterol specific activities decayed much more rapidly than cholesterol in the control subject. In contrast, plasma sitosterol and cholesterol specific activity-time curves were similar and decayed more slowly in the sitosterolemic subjects. In the control subject, the total sitotterol pool was 290 mg and was linearly related to low absorption (18 mg/day); whereas the total sitosterol pool was 17 times (4800 mg) and 13 times (3500 mg) larger, respectively, in the sitosterolemic subjects and was expanded out of proportion to increased absorption because of decreased removal. Daily cholesterol turnover and synthesis were markedly reduced in the sitosterolemic subjects. In four sitosterolemic subjects, plasma concentrations of total sterols, low density lipoproteins, and apolipoprotein B were increased, while those of high density lipoproteins and apolipoprotein A-I were low to normal. The low density lipoproteins were very similar to those of normal control subjects in density distribution, peak flotation rate, sterol-to-protein (apolipoprotein B) ratio, particle size, and morphology. These results demonstrate in patients with sitosterolemia with xanthomatosis that: 1) the absorption of sitosterol and cholesterol is enhanced; 2) tissue recognition between cholesterol and sitosterol is lost; 3) total exchangeable sitosterol pools are expanded out of proportion to absorption because of decreased excretion; 4) plasma sterol and lipoprotein concentrations favor tissue deposition; and 5) cholesterol synthesis is diminished. We postulate that the changes in sitosterol metabolism (increased absorption, loss of tissue sterol structural recognition, expanded pools, and hepatic retention) are a response to reduced cholesterol synthesis in these subject.

Topics: Absorption; Adolescent; Adult; Arteriosclerosis; Cholesterol; Female; Humans; Lipoproteins; Male; Sitosterols; Sterols; Xanthomatosis

14C-labeled C29- and C27-steroids were injected in rats, which were killed after 14 days. Phytosterols (C29) were excreted mainly as such, whereas C27-steroids were recovered essentially as water soluble metabolites. The total 14C-excretion was lower from 3-oxo, delta 4-steroids (5 alpha-stanol precursors) than from 3 beta-hydroxy,delta 5-steroids. 14C-Phytosterols were accumulated more than C27-steroids in liver, serum (mainly in HDL) and especially in adrenal glands and ovaries. In relation to serum, particularly the 5 alpha-stanols were enriched in the adrenal glands and ovaries. No striking lysosomal accumulation of any of the steroids was found.

Topics: Animals; Arteriosclerosis; Blood Proteins; Cricetinae; Female; Injections, Intraperitoneal; Lipid Metabolism, Inborn Errors; Liver; Rats; Rats, Inbred Strains; Sitosterols; Subcellular Fractions; Tissue Distribution

Tissue sterol composition was determined in an 18-year-old male with sitosterolemia with xanthomatosis who died suddenly and whose coronary and aortic vessels showed extensive atherosclerosis and, for comparison, in an 18-year-old male with minimal atherosclerosis who died accidently. Sterols in the control tissues (plasma, erythrocytes, cardiac muscle, lung, liver, aorta, and brain) contained cholesterol with only trace amounts of cholestanol. In contrast, sterols in corresponding tissues of the sitosterolemic subject (except brain) were composed of cholesterol, increased amounts of plant sterols, campesterol and sitosterol, and 5 alpha-saturated stanols, cholestanol, 5 alpha-campestanol, and 5 alpha-sitostanol, that were deposited in approximately the same ratio as present in plasma. However, sitosterolemic brain sterol composition resembled that of the control brain with cholesterol and only trace amounts (less than 1%) of cholestanol and phytosterols. The sitosterolemic aorta was extensively atherosclerotic and contained more than twice the quantity of sterols as the control aorta (5.6 mg/g versus 2.6 mg/g) with increased amounts of cholesterol, plant sterols, and 5 alpha-saturated stanols. These results indicate that cholesterol, plant sterols, and 5 alpha-stanols are deposited prematurely and are associated with accelerated atherosclerosis in subjects with sitosterolemia with xanthomatosis.

Topics: Adolescent; Adult; Aorta; Arteriosclerosis; Coronary Vessels; Female; Humans; Lipid Metabolism, Inborn Errors; Male; Middle Aged; Myocardial Infarction; Sitosterols; Sterols; Xanthomatosis

The antihypercholesterolemic activity of beta-sitosterol and beta-sitostanol was compared in male rabbits given a cholesterol-supplemented diet. beta-Sitosterol and beta-sitostanol were fed to these rabbits at the 0.5% level with cholesterol (0.5% and 0.2% in experiments I and II, respectively). The serum cholesterol level tended to be lower in rabbits fed beta-sitostanol than in the animals fed beta-sitosterol even in experiment I. The beta-sitostanol exhibited a significantly greater hypocholesterolemic activity in experiment II, LDL-cholesterol being decreased markedly. The liver cholesterol decreased in both groups of rabbits to a similar extent. beta-Sitostanol prevented more effectively the formation of dietary cholesterol-induced atheroma in the abdominal aorta than beta-sitosterol. It is most likely, together with the data reported previously on rats, that the hypocholesterolemic activity of beta-sitostanol results from the significantly greater inhibitory effect on the intestinal absorption of cholesterol than that of beta-sitosterol.

Topics: Animals; Anticholesteremic Agents; Arteriosclerosis; Cholesterol; Cholesterol, Dietary; Lipids; Lipoproteins; Liver; Male; Rabbits; Sitosterols; Sterols

Topics: Arteriosclerosis; Aspirin; Cholestyramine Resin; Clofibrate; Dextrothyroxine; Dipyridamole; Humans; Hyperlipidemias; Hypolipidemic Agents; Intracranial Arteriosclerosis; Nicotinic Acids; Sitosterols; Sulfinpyrazone

Topics: Animals; Aorta; Arteriosclerosis; Carboxylic Ester Hydrolases; Cholesterol Esters; Clofibrate; Dextrothyroxine; Dietary Fats; Hypolipidemic Agents; Nicotinic Acids; Oils; Sitosterols; Sterol Esterase

Due to the experimental importance of being able to assess cholesterol absorption during the study of atherogenesis in primates, the plasma isotope ratio technique developed for rats by Zilversmit (7) was tested in New and Old World monkeys and compared with a more cumbersome procedure involving fecal collection and analysis. Although fecal analysis demonstrated an unaccountable loss of the intubated isotope, the comparability of the plasma ratios to absorption calculated by other methods suggest that this techique is probably as reliable as any presently available. The loss of isotope may reflect the absence of dietary cholesterol.

Topics: Animals; Arteriosclerosis; Carbon Radioisotopes; Cholesterol; Cholesterol, Dietary; Feces; Female; Haplorhini; Isotope Labeling; Macaca mulatta; Male; Methods; Sitosterols; Tritium

Topics: Adult; Arteriosclerosis; Cholesterol; Cholestyramine Resin; Clofibrate; Coronary Disease; Electrophoresis, Polyacrylamide Gel; Humans; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Lipid Mobilization; Lipoproteins; Male; Middle Aged; Myocardial Infarction; Phospholipids; Sitosterols; Triglycerides

Topics: Anticholesteremic Agents; Arteriosclerosis; Cholesterol; Geriatrics; Humans; Lipids; Lipoproteins; Sitosterols; Sterols

Topics: Arteriosclerosis; Blood Chemical Analysis; Cholesterol; Fatty Acids; Fatty Acids, Unsaturated; Geriatrics; Humans; Lipids; Pharmacology; Sitosterols; Sterols

Topics: Arteriosclerosis; Cholesterol; Humans; Hypercholesterolemia; Sitosterols; Sterols

Topics: Arteriosclerosis; Cholesterol; Estradiol; Hormones; Humans; Sitosterols; Sterols; Testosterone; Triiodothyronine; Vitamins

Topics: alpha-Linolenic Acid; Animals; Aorta; Arachidonic Acid; Arteriosclerosis; Cholesterol; Dogs; Estradiol; Hypercholesterolemia; Lipid Metabolism; Lipids; Sitosterols; Sterols

Topics: Animals; Arteriosclerosis; Diet; Humans; Hypercholesterolemia; Rats; Sitosterols; Steroids; Thiouracil

Topics: Animals; Arteries; Arteriosclerosis; Cholesterol; Diet; Fats; Humans; Hypercholesterolemia; Rats; Sitosterols; Steroids; Thiouracil

Topics: Arteriosclerosis; Atherosclerosis; Diet; Sitosterols; Steroids

Topics: Arteriosclerosis; Cholesterol; Diet; Diet, Fat-Restricted; Fats; Humans; Lipoproteins; Sitosterols; Steroids

Topics: Arachidonic Acid; Arteriosclerosis; Atherosclerosis; Cholesterol; Humans; Hypercholesterolemia; Safflower Oil; Sitosterols; Steroids

Topics: Arteriosclerosis; Sitosterols; Steroids

Topics: Animals; Arteriosclerosis; Cholesterol; Hypertension; Plaque, Atherosclerotic; Rabbits; Sitosterols; Steroids

Topics: Animals; Arteriosclerosis; Atherosclerosis; Cholestanol; Cholesterol; Rabbits; Sitosterols; Steroids

Topics: Animals; Arteriosclerosis; Atherosclerosis; Cholesterol; Rabbits; Sitosterols; Steroids