Cholesterol Journal Articles

Record 4321 to 4340

Differences in cholesterol metabolism in juvenile baboons are programmed by breast- versus formula-feeding
Mott, G. E., E. M. Jackson, et al. (1995), J Lipid Res 36(2): 299-307.
Abstract: We estimated the effects of breast- and formula-feeding on cholesterol and bile acid metabolism for 1.5 years after weaning in 35 newborn baboons that were breast-fed (n = 12) or fed one of two formulas with high (n = 11) or low (n = 12) polyunsaturated/saturated (P/S) fatty acid composition. Infants were weaned at 15 weeks to a high cholesterol, saturated fat diet. Because formula P/S ratio did not affect any variable for 1.5 years after weaning, the data were averaged for the two formula groups. After weaning, serum cholesterol and lipoprotein cholesterol concentrations among the infant diet groups were not different until after 52 weeks of age. From 70 to 97 weeks of age, serum cholesterol and high density lipoprotein-2 (HDL2)-cholesterol (HDL2-C) concentrations were lower (P < 0.04) among baboons that were breast-fed as infants compared with those fed formulas. We observed no significant postweaning differences in low density lipoprotein (LDL)-C, HDL3-C, or serum apolipoprotein A-I, B, or E concentrations. At 97 weeks of age baboons that were breast-fed until 15 weeks compared with those formula-fed had a 25% lower total bile acid synthetic rate (36.6 vs. 48.6 mumol/day per kg body weight, P < 0.02) due principally to a 29% lower cholic acid synthetic rate (23.2 vs 32.5 mumol/day per kg body weight, P < 0.004). Baboons breast-fed as infants had a 44% higher hepatic LDL-receptor mRNA concentration than those formula-fed (1.45 vs. 1.01 pg mRNA/micrograms total RNA, P < 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox
Artaud-Wild, S. M., S. L. Connor, et al. (1993), Circulation 88(6): 2771-9.
Abstract: BACKGROUND. For decades, the coronary heart disease (CHD) mortality rate has been four or more times higher in Finland than in France despite comparable intakes of dietary cholesterol and saturated fat. A potential answer to this paradox is provided by this study of 40 countries and the analyses of other nutrients in the diets besides cholesterol and saturated fat. METHODS AND RESULTS. CHD death rates for men aged 55 to 64 years were derived from the World Health Organization annual vital statistics. Dietary intakes were gathered from the Food and Agriculture Organization of the United Nations database. Forty countries at various levels of economic development and 40 dietary variables were investigated, including a lipid score that combined the intakes of cholesterol and saturated fat (Cholesterol-Saturated Fat Index CSI). The CSI was significantly and positively related to CHD mortality in the 40 countries. The countries with low CSIs had low CHD death rates. Countries with high CSIs had a wide range of CHD death rates. France, Finland, and other Western industrialized countries had similar CSIs. After adjusting for cholesterol and saturated fat, milk and many components of milk (butterfat, milk protein, calcium from milk, and riboflavin) and total calcium remained positively related to CHD mortality for all 40 countries. There were differences in the consumption of these foods and nutrients in France and Finland. Milk and butterfat (fat from milk, cream, cheese, and butter) consumption was higher in Finland than in France. The consumption of plant foods, recently shown to be protective against CHD (vegetables and vegetable oils containing monounsaturated and polyunsaturated fatty acids), was greater in France than in Finland. CONCLUSIONS. Over the years, France and Finland, with similar intakes of cholesterol and saturated fat, consistently have had very different CHD mortality rates. This paradox may be explained as follows. Given a high intake of cholesterol and saturated fat, the country in which people also consume more plant foods, including small amounts of liquid vegetable oils, and more vegetables (more antioxidants) had lower rates of CHD mortality. On the other hand, milk and butterfat were associated with increased CHD mortality, possibly through their effects on thrombosis as well as on atherosclerosis.

Differences in erythrocyte membrane cholesterol to phospholipids ratio in postmenopausal women with and without hormone replacement
Piazze Garnica, J. J., M. M. Anceschi, et al. (1997), Eur J Obstet Gynecol Reprod Biol 72(2): 191-4.
Abstract: OBJECTIVES: To investigate the changes in the cholesterol:phospholipids (C/PL) ratio of erythrocyte membrane in post-menopausal women with and without hormone replacement therapy (HRT). STUDY DESIGN: A cross-sectional study including 83 patients divided into three groups according to HRT (group 1, no HRT (n = 52); group 2, combined HRT (n = 16); and group 3, estrogen-only therapy (n = 15)). RESULTS: The C/PL ratio was lower in group 2 with respect to group 1 and group 3 (P = 0.03). No difference was found in erythrocyte membrane cholesterol between the three groups; however, the phospholipid concentration was higher in group 2 with respect to the other groups (P < 0.05). In the control group, C/PL values correlated positively with plasma LDL levels (P < 0.005) and negatively with HDL levels (P < 0.005). CONCLUSIONS: From our data the addition of progestogens in HRT appears to decrease the C/PL of the erythrocyte membrane possibly resulting in a beneficial effect on rheological properties of erythrocyte membrane. The results of our study thus suggest additional benefits from supplementation of progestogens in HRT, in addition to prevention of estrogen dependent endometrial hyperplasia and adenocarcinoma.

Differences in HDL cholesterol concentrations in Japanese, American, and Australian children
Dwyer, T., H. Iwane, et al. (1997), Circulation 96(9): 2830-6.
Abstract: BACKGROUND: Mortality from coronary heart disease is relatively low in Japan compared with other developed countries and has remained low despite an increasing standard of living and an apparent increase in mean plasma cholesterol concentration in adults over the past three decades. Important differences in childhood plasma lipoprotein profile might contribute to some of the difference in coronary heart disease mortality seen between Japan and both Australia and North America. METHODS AND RESULTS: Plasma HDL cholesterol and total cholesterol were surveyed in representative populations of schoolchildren in Australia, Japan, and Bogalusa, La. The mean concentration of plasma HDL cholesterol (but not total cholesterol) was higher for Japanese schoolchildren than for Australian or US schoolchildren (P<.001). In addition, the difference in plasma HDL cholesterol between the ages of 8 to 10 years and 12 to 15 years was much greater for Australian (boys, 15.2%; girls, 2.6%) and US (boys, 9.1%; girls, 2.7%) children than for their Japanese counterparts (boys, 4.2%; girls, 1.9%). An examination of potential explanatory factors revealed little difference in body mass index between samples, higher physical activity levels for the Japanese compared with the Australians, and substantial differences in dietary intake between Japanese and Australian schoolchildren. CONCLUSIONS: The relatively high ratio of plasma HDL cholesterol to total cholesterol in Japanese schoolchildren and the relatively small negative difference of plasma HDL cholesterol with age may help to explain why the coronary heart disease mortality rate in Japan is low compared with that in other developed countries.

Differences in HDL-cholesterol:apoA-I + apoA-II ratio and apoE phenotype with albuminuric status in Type I diabetic patients
Soedamah-Muthu, S. S., H. M. Colhoun, et al. (2000), Diabetologia 43(11): 1353-9.
Abstract: AIMS/HYPOTHESIS: To examine whether the HDL-cholesterol:apoA-I + apoA-II ratio and the epsilon2 allele are related to albuminuria at baseline and whether they are risk factors for progression of albuminuria in a cohort study of patients with Type I (insulin-dependent) diabetes mellitus. METHODS: At baseline, the study cohort comprised 617 patients, aged 15-60 years, from seven European diabetic centres of the EURODIAB study. Albumin excretion rate, measured in a central laboratory, was categorised as normoalbuminuria at 20 microg/min or less, microalbuminuria between 20 and 200 microg/min or macroalbuminuria at 200 microg/min or over. Of the 250 patients who were normoalbuminuric at baseline and had follow-up albuminuria measurements, 34 patients were defined as early progressors. RESULTS: At baseline, the mean HDL-cholesterol:apoA-I + apoA-II ratio was lower in macroalbuminuric patients (0.79, 95 % CI:0.74-0.83) compared with normoalbuminuric (0.88, 95 % CI:0.87-0.90) patients (p = 0.0002, adjusted for age and sex). At follow-up, 34 patients who progressed from normoalbuminuria to microalbuminuria or macroalbuminuria also had a slightly lower baseline ratio (0.85, 95% CI:0.80-0.89) than those 216 who remained normoalbuminuric (0.89, 95 % CI:0.87-0.92) (adjusted p = 0.08). Neither of these relations were independent of LDL-cholesterol or fasting triglyceride. There was no association of the epsilon2 allele with albuminuria either at baseline (OR = 1.4, 95% CI:0.7-2.8) or with progression of albuminuria (OR = 0.4, 95 % CI:0.1-3.5). CONCLUSION/INTERPRETATION: There is an inverse relation of HDL-cholesterol:apoA-I + apoA-II ratio with albuminuria at baseline. This lower ratio in microalbuminuric or macroalbuminuric patients could contribute to the increased risk of cardiovascular disease associated with nephropathy. There is weak evidence that HDL-composition is a risk factor for progression of albuminuria and no association of the epsilon2 allele with diabetic nephropathy.

Differences in propionate-induced inhibition of cholesterol and triacylglycerol synthesis between human and rat hepatocytes in primary culture
Lin, Y., R. J. Vonk, et al. (1995), Br J Nutr 74(2): 197-207.
Abstract: Propionate is a short-chain fatty acid formed in the colon and supposedly involved in the cholesterol-lowering effect of soluble fibre. To explore the underlying mechanism(s) of this fibre action, we have used human hepatocytes in primary culture to study the effects of propionate on hepatic lipid synthesis. Initial experiments with mevalonate and mevinolin, a competitive inhibitor of hydroxymethylglutaryl (HMG)-CoA reductase (EC 1.1.1.88) were performed to evaluate basic regulatory mechanisms in these cells; results were compared with those obtained with rat hepatocytes. Incubation for 24 h with mevalonate caused a similar, concentration-dependent inhibition of 14Cacetate incorporation into cholesterol in human and rat hepatocytes. Likewise, mevinolin (100 mumol/l) inhibited the formation of cholesterol from radiolabelled acetate by about 80% in cells from both species. Propionate inhibited cholesterol as well as triacylglycerol synthesis from 14Cacetate with a similar concentration-dependency in rat hepatocytes. Fifty percent inhibition was obtained at a propionate concentration of only 0.1 mmol/l. This propionate-induced inhibition was not affected by a 100-fold excess of unlabelled acetate. Human hepatocytes were much less susceptible in this respect: propionate concentrations of 10-20 mmol/l were required to obtain similar inhibitory effects in these cells, i.e. values greatly exceeding reported portal propionate concentrations in humans. The results suggest the existence of differences in the regulation of hepatic cholesterol (and triacylglycerol) synthesis between human and rat liver cells. These results do not support the hypothesis that the fibre-induced decrease in plasma cholesterol concentration in man is mediated by a direct effect of propionate on hepatic cholesterol synthesis.

Differences in the frequency of cholesterol screening in patients with Medicaid compared with private insurance
Hueston, W. J., E. Spencer, et al. (1995), Arch Fam Med 4(4): 331-4.
Abstract: OBJECTIVE: To assess compliance with preventive screening for Medicaid recipients compared with individuals with equal access to preventive services. SETTING: A community-based family practice residency program. METHODS: Survey of a consecutive sample of English-reading individuals, aged 18 to 50 years, with Medicaid (n = 98) or private insurance (n = 75), who had scheduled appointments in the clinic. MAIN RESULTS: Patients with Medicaid were as likely as those with private insurance to be screened for hypertension and cervical cancer in the last 5 years but were less likely to have received cholesterol screening (39% vs 65%, P <.001). Even after adjusting for differences in gender composition, age, race, marital status, and education level attained, patients with Medicaid were still less likely to have received cholesterol screening (odds ratio, 0.43; 95% confidence interval, 0.21 to 0.57). Although patients with Medicaid were no more likely to identify a barrier and, when identifying barriers, did not identify significantly more barriers than patients with private insurance, Medicaid recipients were less likely to state that cholesterol testing had been recommended by their physician (30% vs 44%, P =.05). CONCLUSIONS: Because access to screening tests by patients with Medicaid is equal to or better than that of those with insurance, differences in the frequency of cholesterol screening should not reflect financial barriers. Differences in the attention paid to screening by physicians and differences in cultural beliefs about the importance of screening may play a role in the underuse of screening services by individuals in lower socioeconomic groups.

Differences in the modulation of collective membrane motions by ergosterol, lanosterol, and cholesterol: a dynamic light scattering study
Hildenbrand, M. F. and T. M. Bayerl (2005), Biophys J 88(5): 3360-7.
Abstract: A dynamic light scattering setup was used to study the undulations of freely suspended planar lipid bilayers, the so-called black lipid membranes, over a previously inaccessible range of frequency and wave number. A pure synthetic lecithin bilayer, 1,2-dielaidoyl-sn-3-glycero-phoshatidylcholine (DEPC), and binary mixtures of DEPC with 40 mol % of cholesterol, ergosterol, or lanosterol were studied. By analyzing the dynamic light scattering data (oscillation and damping curves) in terms of transverse shear motion, we extracted the lateral tension and surface viscosity of the composite bilayers for each sterol. Cholesterol gave the strongest increase in lateral tension (approximately sixfold) with respect to the DEPC control, followed by lanosterol (approximately twofold), and ergosterol (1.7-fold). Most interestingly, only cholesterol simultaneously altered the surface viscosity of the bilayer by almost two orders of magnitude, whereas the other two sterols did not affect this parameter. We interpret this unique behavior of cholesterol as a result of its previously established out-of-plane motion which allows the molecule to cross the bilayer midplane, thereby effectively coupling the bilayer leaflets to form a highly flexible but more stable composite membrane.

Different cholesterol deposition in aorta of Dahl salt-sensitive rats and spontaneously hypertensive rats fed a high-cholesterol diet
Yamaguchi, Y., S. Kitagawa, et al. (1995), Clin Exp Pharmacol Physiol Suppl 22(1): S249-50.
Abstract: 1. We compared the serum and aortic lipid levels in spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats (DSR) fed a high-cholesterol (HC) diet. 2. In SHR fed the HC diet, the serum cholesterol level significantly increased, but no aortic cholesterol deposition was observed. 3. The serum cholesterol level in DSR fed the HC diet markedly increased compared to that in DSR fed the basal diet, and this change was greater with the diet containing 8% NaCl than 0.4% NaCl. A significant increase in the content of aortic cholesterol, notably cholesteryl ester, was observed in only DSR fed the HC diet containing 8% NaCl. 4. These results suggest that the combination of hypercholesterolaemia with salt-induced hypertension acts as a greater risk factor for atherosclerosis than that with genetic hypertension.

Different clinical and coronary angiographic findings according to ratios of total cholesterol to high-density lipoprotein cholesterol during the acute phase of myocardial infarction
Kosuge, M., K. Kimura, et al. (2004), J Cardiol 43(6): 251-8.
Abstract: OBJECTIVES: Several pathological studies have shown that a higher ratio of the serum total cholesterol concentration to the high-density lipoprotein cholesterol concentration (TC/HDL-C ratio) is associated with plaque rupture in patients with acute coronary syndromes. We examined the relationship between the serum total cholesterol concentration and the TC/HDL-C ratio, and clinical and angiographic findings in patients with first acute myocardial infarction. METHODS: Two hundred eighty patients were classified into quartiles according to the TC/HDL-C ratio measured within 24 hr from symptom onset: 70 patients in the first quartile (group L: mean TC/HDL-C ratio, 3.0), 140 in the second and third quartiles (group M: mean TC/HDL-C ratio, 4.6), and 70 in the fourth quartile (group H: mean TC/HDL-C ratio, 7.5). RESULTS: There were no differences among the three groups with regard to sex, diabetes mellitus or hypertension. Patients in group L were older (66 +/- 9 vs 60 +/- 11, 56 +/- 10 years, p < 0.01) and had a higher incidence of stable angina before acute myocardial infarction (26% vs 14%, 10%, p < 0.05) than in patients groups M and H. Although coronary angiograms revealed no difference in the number of diseased vessels among the three groups, extent index indicating the proportion of each coronary segment that appears angiographically abnormal was lowest in group L (0.7 +/- 0.5), followed by group M (1.3 +/- 0.6), and high- est in group H (1.7 +/- 0.6, p < 0.01). The number of segments with calcification and the incidence of calcification in the culprit lesion were higher in group L than in groups M and H. CONCLUSIONS: Our findings suggest that the clinical presentations and angiographic appearances differ according to the TC/HDL-C ratio in the acute phase of acute myocardial infarction.

Different effect of Intralipid and triacylglycerol rich lipoproteins on the Kodak Ektachem serum cholesterol determination
Cobbaert, C. and A. Tricarico (1993), Eur J Clin Chem Clin Biochem 31(2): 107-9.
Abstract: We documented the quantitative effects of lipaemia on cholesterol recovery on a Kodak Ektachem 700 XRC analyser (Rochester, NY, USA) in comparison with a Hitachi 717 analyser (Boehringer, Mannheim, Germany). Using the linear ranges of the analysers, we compared the effects of adding Intralipid and of adding high concentrations of native Very-Low-Density-Lipoproteins and/or chylomicrons. Our data demonstrate less than 10% bias for the Kodak cholesterol determination in an Intralipid dilution series prepared according to M. R. Glick and coworkers (e.g. Clin. Chem. 33 (1987) 1453-1458). However, in a hypertriglyceridaemic dilution series (theoretical cholesterol concentrations ranged from 5.2 to 15.5 mmol/l) the Kodak cholesterol recovery fraction decreased from 0.88 to 0.58 when the triacylglycerol concentration increased from 5.64 mmol/l to 38.35 mmol/l. In contrast, the cholesterol recoveries on the Hitachi analyser were complete for both approaches. We conclude that the lipaemia effect on the Kodak cholesterol determination is not adequately reflected by addition of Intralipid, because the Kodak cholesterol determination is more prone to interference by turbidity when triacylglycerols are presented as native serum lipoproteins, especially as chylomicrons.

Different effect of simvastatin and atorvastatin on key enzymes involved in VLDL synthesis and catabolism in high fat/cholesterol fed rabbits
Verd, J. C., C. Peris, et al. (1999), Br J Pharmacol 127(6): 1479-85.
Abstract: The effects of atorvastatin (3 mg kg(-1)) and simvastatin (3 mg kg(-1)) on hepatic enzyme activities involved in very low density lipoprotein metabolism were studied in coconut oil/cholesterol fed rabbits. Plasma cholesterol and triglyceride levels increased 19 and 4 fold, respectively, after 7 weeks of feeding. Treatment with statins during the last 4 weeks of feeding abolished the progression of hypercholesterolaemia and reduced plasma triglyceride levels. 3-Hydroxy-3-methyl-glutaryl Coenzyme A reductase, acylcoenzyme A:cholesterol acyltransferase, phosphatidate phosphohydrolase and diacylglycerol acyltransferase activities were not affected by drug treatment. Accordingly, hepatic free cholesterol, cholesteryl ester and triglyceride content were not modified. Simvastatin treatment caused an increase (72%) in lipoprotein lipase activity without affecting hepatic lipase activity. Atorvastatin caused a reduction in hepatic phospholipid content and a compensatory increase in CTP:phosphocholine cytidylyl transferase activity. The results presented in this study suggest that, besides the inhibitory effect on 3-hydroxy-3-methyl-glutaryl Coenzyme A reductase, simvastatin and atorvastatin may have additional effects that contribute to their triglyceride-lowering ability.

Different effects of a high-cholesterol diet on ischemic cardiac dysfunction and remodeling induced by coronary stenosis and coronary occlusion
Yaoita, H., K. Yoshinari, et al. (2005), J Am Coll Cardiol 45(12): 2078-87.
Abstract: OBJECTIVES: The aim of the study was to assess whether and how the high-cholesterol diet (HCD)-related worsening of heart failure differs between coronary stenosis (CS)-induced myocardial ischemia and coronary occlusion-induced myocardial infarction (MI). BACKGROUND: An HCD, a risk factor for coronary artery disease, also worsens ischemic heart failure. Although accelerated coronary plaque formation may be a cause of this, other mechanism(s), such as its effects through the coronary microcirculation, remain to be clarified. METHODS: In rats fed a normal chow diet or HCD, CS or MI was created surgically, and we assessed left ventricular (LV) function by echocardiography and myocardial inflammation by histopathology. In the CS groups, CS severity by histopathology, myocardial perfusion by microspheres, myocardial protein kinase C (PKC) translocation by Western blotting, and myocardial endothelial nitric oxide (NO) function were also investigated by the in vitro myocardial oxygen consumption method. RESULTS: Coronary stenosis impaired myocardial endothelial NO function and reduced coronary flow reserve, evoking myocardial ischemia, as shown by PKC- activation, myocardial inflammation, fibrosis, cardiac dysfunction, and remodeling. By itself, HCD greatly augmented such CS-induced myocardial abnormalities without modulating the CS severity. Such detrimental effects of HCD were ameliorated by supplying a cofactor of endothelial NO synthase-tetrahydrobiopterin. In contrast, MI-induced heart failure was not aggravated by HCD. CONCLUSIONS: The CS-induced ischemic myocardium seems to be more susceptible to the pro-inflammatory effect of HCD than infarcted myocardium, leading to aggravation of LV dysfunction and remodeling via modification of the coronary circulation downstream of the epicardial CS site, partly through impairment of endothelial NO.

Different effects of soy protein on cholesterol metabolism in rats and mice
Yamashita, J., Y. Fujita, et al. (1990), Monogr Atheroscler 16: 36-43.

Different effects of subclasses of HDL containing apoA-I but not apoA-II (LpA-I) on cholesterol esterification in plasma and net cholesterol efflux from foam cells
Ohta, T., K. Saku, et al. (1995), Arterioscler Thromb Vasc Biol 15(7): 956-62.
Abstract: We investigated the effects of subclasses of plasma LpA-I (HDL containing apoA-I but not apoA-II) on cholesterol esterification in plasma and net cholesterol efflux from foam cells. LpA-I was composed of particles of three diameters: large (11.1 nm; Lg-LpA-I), medium (8.8 nm; Md-LpA-I), and small (7.7 nm; Sm-LpA-I). Plasma concentrations of LpA-I were positively correlated only with the level of Lg-LpA-I. Plasma concentrations of Lg-LpA-I were inversely correlated with the rate of cholesterol esterification in plasma and VLDL- and LDL-depleted plasma. Plasma concentrations of Md-LpA-I and Sm-LpA-I did not correlate with the rate of cholesterol esterification in plasma or VLDL- and LDL-depleted plasma. When macrophage foam cells were incubated with Md- and Sm-LpA-I, cellular cholesterol mass was reduced by approximately 70%. In contrast, the cellular cholesterol-reducing capacity of Lg-LpA-I was negligible. Lg-LpA-I inhibited net cholesterol removal from foam cells that was mediated by Md- and Sm-LpA-I and cholesteryl ester production with these particles. These results suggest that Md- and Sm-LpA-I may actively participate in cellular cholesterol removal and cholesterol esterification in plasma and HDL, while Lg-LpA-I may regulate these functions of Md- and Sm-LpA-I.

Different effects of the hypolipidemic drugs pravastatin and lovastatin on the cholesterol biosynthesis of the human ocular lens in organ culture and on the cholesterol content of the rat lens in vivo
de Vries, A. C. and L. H. Cohen (1993), Biochim Biophys Acta 1167(1): 63-9.
Abstract: This study aimed to investigate the influence of the hypocholesterolemic drugs pravastatin and lovastatin on the cholesterol biosynthesis in the ocular lens. Two model systems were used: a human lens organ culture system and an in vivo rat lens system. For measurements of cholesterol and fatty acid synthesis rates, human lenses were incubated for 20 h in the presence of 14Cacetate. Pravastatin and lovastatin were added 1 h prior to the addition of the radioactive label. In order to avoid the influence of differences relating to individual donors, one lens from each donor was incubated without drug (control) and the other lens was incubated in the presence of the drug. Statistical analysis showed that the fatty acid synthesis rate was not influenced by the drug. For each lens pair the percentage inhibition of the cholesterol synthesis caused by the drug was calculated. Using various concentrations of the drugs, a dose-response curve was composed for the inhibition of the cholesterol synthesis. The experiments showed that in the human lens organ culture system, lovastatin was 100-fold more potent than pravastatin in inhibiting the cholesterol biosynthesis. To study the in vivo influence of vastatins on the cholesterol content of the developing lens, Wistar rats were weaned at day 21 of age and subsequently the pups were fed a control diet or drug-containing diet (10, 50 or 100 mg lovastatin/kg chow) for a 3-week period. At the end of diet intervention, doses of 50 or 100 mg lovastatin/kg chow had caused a reduction of about 20% of the lenticular cholesterol content compared with controls. No effect on the lens cholesterol content by pravastatin was observed. Both human ex vivo and rat in vivo experiments show that lovastatin much more strongly inhibits the lenticular cholesterol synthesis than does pravastatin.

Different feedback regulation of hepatic cholesterol and bile acid synthesis by glycodeoxycholic acid in rabbits
Xu, G., G. Salen, et al. (1993), Gastroenterology 105(4): 1192-9.
Abstract: BACKGROUND: To explore the sexual difference in the feedback regulation of hepatic bile acid synthesis, glycodeoxycholic acid (GDCA) was administered to 15 male and 14 female rabbits. METHODS: After bile diversion, GDCA equivalent to the hepatic bile acid influx was infused intraduodenally. Biliary cholic acid output represented bile acid synthesis. Hepatic 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7 alpha-hydroxylase activities and steady state messenger RNA (mRNA) levels were determined. RESULTS: GDCA inhibited bile acid synthesis less in female than in male rabbits. Hepatic HMG-CoA reductase activity decreased 39% in males, but increased 48% in females. Hepatic cholesterol 7 alpha-hydroxylase activity decreased similarly in males and females, and mRNA levels decreased 86% in males but were unchanged in females. CONCLUSIONS: (1) Total bile diversion stimulated both hepatic cholesterol and bile acid synthesis by activating the rate-controlling enzymes and increasing mRNA levels. (2) GDCA decreased mRNA levels of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in males, but mRNA levels did not decrease in females. (3) Bile acid synthesis was sustained in females because continued biosynthesis of cholesterol provided a substrate for cholesterol 7 alpha-hydroxylase and stimulus for enzyme formation.

Different mechanisms of uptake of stearic acid and cholesterol into rabbit jejunal brush border membrane vesicles
Burdick, S., M. Keelan, et al. (1993), Lipids 28(12): 1063-7.
Abstract: The rate of uptake of stearic acid and cholesterol solubilized in taurocholic acid (TC) was examined in rabbit jejunal brush border membrane vesicles (BBMV). For stearic acid (18:0) or cholesterol there was an initial rapid rate of uptake, which reached a plateau within approximately 1 min and remained stable thereafter. At low concentrations of 18:0 and 20 mM, but not 2 mM, TC, there was a curvilinear relationship between the concentration of 18:0 and uptake, whereas the relationship between cholesterol uptake and concentration was linear over a wide range of values. When the concentration of TC was held constant at increasing concentrations of 18:0 or cholesterol, there was a linear increase in the rate of uptake. When the concentration of 18:0 or cholesterol was held constant and the concentration of TC was increased from 2 to 20 mM, the uptake of 18:0 declined, but the rate of uptake of cholesterol increased. When the concentrations of 18:0 plus TC, or cholesterol plus TC, were both increased in unison and their ratio was held constant, their rate of uptake increased. Thus, (i) BBMV may be used to assess the rate of uptake of lipids; (ii) the partitioning of cholesterol from bile acid micelles into the BBMV appears to be by way of "collision" of the cholesterol with the membrane. In contrast, the uptake of 18:0 from the micelle into the membrane vesicles may be by both the collision and the aqueous/dissociation models; and (iii) 18:0 uptake may be mediated by both a concentration-dependent and a concentration-independent component.(ABSTRACT TRUNCATED AT 250 WORDS)

Different risk factors for different stroke subtypes: association of blood pressure, cholesterol, and antioxidants
Leppala, J. M., J. Virtamo, et al. (1999), Stroke 30(12): 2535-40.
Abstract: BACKGROUND AND PURPOSE: Blood pressure is an important risk factor for stroke, but the roles of serum total and HDL cholesterol, alpha-tocopherol, and beta-carotene are poorly established. We studied these factors in relation to stroke subtypes. METHODS: Male smokers (n=28 519) aged 50 to 69 years without a history of stroke participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a controlled trial to test the effect of alpha-tocopherol and beta-carotene supplementation on cancer. From 1985 to 1993, a total of 1057 men suffered from primary stroke: 85 had subarachnoid hemorrhage; 112, intracerebral hemorrhage; 807, cerebral infarction; and 53, unspecified stroke. RESULTS: Systolic blood pressure > or = 160 mm Hg increased the risk of all stroke subtypes 2.5 to 4-fold. Serum total cholesterol was inversely associated with the risk of intracerebral hemorrhage, whereas the risk of cerebral infarction was raised at concentrations > or = 7.0 mmol/L. The risks of subarachnoid hemorrhage and cerebral infarction were lowered with serum HDL cholesterol levels > or = 0.85 mmol/L. Pretrial high serum alpha-tocopherol decreased the risk of intracerebral hemorrhage by half and cerebral infarction by one third, whereas high serum beta-carotene doubled the risk of subarachnoid hemorrhage and decreased that of cerebral infarction by one fifth. CONCLUSIONS: The risk factor profiles of stroke subtypes differ, reflecting different etiopathology. Because reducing atherosclerotic diseases, including ischemic stroke, by lowering high serum cholesterol is one of the main targets in public health care, further studies are needed to distinguish subjects with risk of hemorrhagic stroke. The performance of antioxidants needs confirmation from clinical trials.

Different sphingolipids show differential partitioning into sphingolipid/cholesterol-rich domains in lipid bilayers
Wang, T. Y. and J. R. Silvius (2000), Biophys J 79(3): 1478-89.
Abstract: Two fluorescence-based approaches have been applied to examine the differential partitioning of fluorescent phospho- and sphingolipid molecules into sphingolipid-enriched domains modeling membrane "lipid rafts." Fluorescence-quenching measurements reveal that N-(diphenylhexatrienyl)propionyl- (DPH3:0-)-labeled gluco- and galactocerebroside partition into sphingolipid-enriched domains in sphingolipid/phosphatidylcholine/cholesterol bilayers with substantially higher affinity than do analogous sphingomyelin, ceramide, or phosphatidylcholine molecules. By contrast, the affinity of sphingomyelin and ceramide for such domains is only marginally greater than that of a phosphatidylcholine with similar hydrocarbon chains. By using direct measurements of molecular partitioning between vesicles of different compositions, we show that the relative affinities of different C(6)-NBD- and C(5)-Bodipy-labeled sphingolipids for sphingolipid-enriched domains are quantitatively, and in most circumstances even qualitatively, quite different from those found for species whose N-acyl chains more closely resemble the long saturated chains of cellular sphingolipids. These findings lend support in principle to previous suggestions that differential partitioning of different sphingolipids into "raft" domains could contribute to the differential trafficking of these species in eukaryotic cells. However, our findings also indicate that short-chain sphingolipid probes previously used to examine this phenomenon are in general ill-suited for such applications.

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Cholesterol Journal Articles