| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effects of endogenous and exogenous cholesterol on the ultrastructure and steroid secretion of undifferentiated rat adrenocortical cells in primary culture Heikkila, P. (1990), Cell Tissue Res 259(3): 421-7. Abstract: The present study was undertaken to define the effects of lipoprotein-derived cholesterol and endogenous, de novo synthesized cholesterol on the ultrastructure and function of undifferentiated rat adrenocortical cells lipoprotein (HDL3 and LDL) receptor-negative, zona glomerulosa-like adrenocortical cells in primary culture. For this purpose human plasma high density lipoprotein (HDL3) or low density lipoprotein (LDL) was added to culture medium devoid of cholesterol. Steroid secretion remained at the low basal level even after addition of lipoproteins, and the amount of intracellular lipid droplets did not increase. When mevinolin (0.96 microgram/ml), an inhibitor of cholesterol synthesis, was added to the culture medium, a low secretion of corticosterone was measured both in serum-free and serum-containing media. Ultrastructurally, lipid droplets disappeared after treatment with mevinolin in both media used. At this concentration of mevinolin cell proliferation was similar to that in the controls, but at higher concentrations (4.8 or 9.6 micrograms/ml) proliferation was inhibited to 42% and 26% in serum-free medium, and 20% and 12% in serum-supplemented medium, respectively. This study demonstrates that cell proliferation and synthesis of corticosterone by undifferentiated rat adrenocortical cells is identical in the absence or presence of exogenous lipoprotein cholesterol. Inhibition of de novo cholesterol synthesis by mevinolin over a period of 7 days does not inhibit corticosterone secretion or proliferation of cells but decreases the amount of intracellular lipid droplets, thus suggesting utilization of intracellular cholesterol esters. However, higher concentrations of mevinolin inhibit proliferation of cells both in serum-free and serum-containing media. |
| Effects of enduracin on the level of cholesterol in flying personnel Preobrazhenskii, V. N. and A. A. Matveev (1997), Aviakosm Ekolog Med 31(3): 43-4. |
| Effects of endurance exercise training on plasma HDL cholesterol levels depend on levels of triglycerides: evidence from men of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study Couillard, C., J. P. Despres, et al. (2001), Arterioscler Thromb Vasc Biol 21(7): 1226-32. Abstract: High density lipoprotein (HDL) cholesterol concentrations have been shown to increase with regular endurance exercise and, therefore, can contribute to a lower risk of coronary heart disease in physically active individuals compared with sedentary subjects. Although low HDL cholesterol levels are frequently observed in combination with hypertriglyceridemia, some individuals may be characterized by isolated hypoalphalipoproteinemia, ie, low HDL cholesterol levels in the absence of elevated triglyceride (TG) concentrations. The present study compared the responses of numerous lipoprotein-lipid variables to a 20-week endurance exercise training program in men categorized on the basis of baseline TG and HDL cholesterol concentrations: (1) low TG and high HDL cholesterol (normolipidemia), (2) low TG and low HDL cholesterol (isolated low HDL cholesterol), (3) high TG and high HDL cholesterol (isolated high TGs), and (4) high TGs and low HDL cholesterol (high TG/low HDL cholesterol). A series of physical and metabolic variables was measured before and after the training program in a sample of 200 men enrolled in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. At baseline, men with high TG/low HDL cholesterol had more visceral adipose tissue than did men with isolated low HDL cholesterol and men with normolipidemia. The 0.4% (not significant) exercise-induced increase in HDL cholesterol levels in men with isolated low HDL cholesterol suggests that they did not benefit from the "HDL-raising" effect of exercise. In contrast, men with high TG/low HDL cholesterol showed a significant increase in HDL cholesterol levels (4.9%, P<0.005). Whereas both subgroups of men with elevated TG levels showed reductions in plasma TGs (approximately -15.0%, P<0.005), only those with high TG/low HDL cholesterol showed significantly reduced apolipoprotein B levels at the end of the study (-6.0%, P<0.005). Multiple regression analyses revealed that the exercise-induced change in abdominal subcutaneous adipose tissue (10.6%, P<0.01) was the only significant correlate of the increase in plasma HDL cholesterol with training in men with high TG/low HDL cholesterol. Results of the present study suggest that regular endurance exercise training may be particularly helpful in men with low HDL cholesterol, elevated TGs, and abdominal obesity. |
| Effects of enrichment of fibroblasts with unesterified cholesterol on the efflux of cellular lipids to apolipoprotein A-I Gillotte-Taylor, K., M. Nickel, et al. (2002), J Biol Chem 277(14): 11811-20. Abstract: This study elucidates the factors underlying the enhancement in efflux of human fibroblast unesterified cholesterol and phospholipid (PL) by lipid-free apolipoprotein (apo) A-I that is induced by cholesterol enrichment of the cells. Doubling the unesterified cholesterol content of the plasma membrane by incubation for 24 h with low density lipoprotein and lipid/cholesterol dispersions increases the pools of PL and cholesterol available for removal by apoA-I from about 0.8-5%; the initial rates of mass release of cholesterol and PL are both increased about 6-fold. Expression of the ATP binding cassette transporter A1 (ABCA1) is critical for this increased efflux of lipids, and cholesterol loading of the fibroblasts over 24 h increases ABCA1 mRNA about 12-fold. The presence of more ABCA1 and cholesterol in the plasma membrane results in a 2-fold increase in the level of specific binding of apoA-I to the cells with no change in binding affinity. Characterization of the species released from either control or cholesterol-enriched cells indicates that the plasma membrane domains from which lipids are removed are cholesterol-enriched with respect to the average plasma membrane composition. Cholesterol enrichment of fibroblasts also affects PL synthesis, and this leads to enhanced release of phosphatidylcholine (PC) relative to sphingomyelin (SM); the ratios of PC to SM solubilized from control and cholesterol-enriched fibroblasts are approximately 2/1 and 5/1, respectively. Biosynthesis of PC is critical for this preferential release of PC and the enhanced cholesterol efflux because inhibition of PC synthesis by choline depletion reduces cholesterol efflux from cholesterol-enriched cells. Overall, it is clear that enrichment of fibroblasts with unesterified cholesterol enhances efflux of cholesterol and PL to apoA-I because of three effects, 1) increased PC biosynthesis, 2) increased PC transport via ABCA1, and 3) increased cholesterol in the plasma membrane. |
| Effects of erythrocytes and serum proteins on lung accumulation of lipoplexes containing cholesterol or DOPE as a helper lipid in the single-pass rat lung perfusion system Sakurai, F., T. Nishioka, et al. (2001), Eur J Pharm Biopharm 52(2): 165-72. Abstract: Plasmid DNA-cationic liposome complexes (lipoplexes) accumulate in the lung to a great extent immediately after intravenous administration, and gene expression occurs predominantly in the lung. However, the detailed mechanisms underlying the lung accumulation of lipoplexes are not fully understood. In this study, we investigated the effect of blood components on the lung accumulation of lipoplexes using a single-pass rat lung perfusion system. Two types of lipoplexes, Chol-containing lipoplex ((32)PDNA-DOTMA/Chol liposome complex) and DOPE-containing lipoplex ((32)PDNA-DOTMA/DOPE liposome complex), pre-incubated with whole blood, serum, or erythrocytes, were injected into the perfused lung via an artery. Similarly to in vivo observations, extensive lung accumulation was observed for both types of lipoplexes after incubation with whole blood during a single passage. The (32)P-labeled lipoplexes pre-incubated with erythrocytes showed similar lung accumulation, whereas their lung accumulation after incubation with serum was significantly reduced, suggesting that erythrocytes would be more responsible blood components for extensive uptake by the perfused lung. However, there was a clear difference in the amounts of the accumulated erythrocytes after intra-arterial injection between the two lipoplex formulations. A significant degree of erythrocyte accumulation was observed when the DOPE-containing lipoplex was injected, whereas the Chol-containing lipoplex failed to induce any significant erythrocyte accumulation in the lung. In vitro experiments showed that the major fraction of both lipoplexes was bound to erythrocytes. These data suggested that Chol-containing lipoplexes bound to erythrocytes before injection dissociate from the erythrocytes and are transferred to the lung capillary endothelial cells during their passage through the lung. In contrast, DOPE-containing lipoplexes bound to erythrocytes cause aggregation and are embolized in the lung capillary with erythrocytes. Thus, the present study demonstrated that the interaction with erythrocytes plays an important role in the lung accumulation of lipoplexes and that neutral helper lipid significantly affects this interaction. |
| Effects of estradiol, cyproterone acetate, tibolone and raloxifene on uterus and aorta atherosclerosis in oophorectomized cholesterol-fed rabbits Sanjuan, A., C. Castelo-Branco, et al. (2003), Maturitas 45(1): 59-66. Abstract: BACKGROUND: Different hormonal replacement regimens are used for treating climacteric complaints; however, not all of them have the same clinical profile. Cardiovascular disease (CVD) is a major health problem and tibolone, raloxifene, estradiol (alone or with cyproterone acetate) have been added to cholesterol-fed rabbits to study atherosclerosis. METHODS: A total of 48 cholesterol-fed New Zealand white rabbits were studied for 4 months. Forty rabbits underwent bilateral ovariectomy and the other eight were sham operated (group S). The ovariectomized rabbits were allocated to five groups of eight animals each receiving tibolone (Group T, 6 mg/day), raloxifene (R, 35 mg/day), estradiol valerate (E, 3 mg/day), estradiol valerate plus cyproterone acetate (EC, 3+0.5 mg/day, respectively), and no treatment for the control group (C). The sham group received no treatment too. RESULTS: After 4 months the percentage of the extent of atherosclerosis in the aorta was 30.4% in C group, 24.5% in S group, 10.2% in T group, 30.3% in R group, 17.9% in E group and 28.1% in EC group (P<0.05 T vs. C, R, EC). The aortic cholesterol content compared with aortic weight was 8.55 microg/mg in C group, 11.97 microg/mg in S group, 1.86 microg/mg in T group, 3.82 microg/mg in R group, 2.86 microg/mg in E group and 5.24 microg/mg in EC group (P<0.05 T vs. EC, C, S; R vs. C, S; E vs. C, S). Uterine weights in grams were: 1.89 (C group), 2.24 (S), 7.38 (T), 1.94 (R), 9.92 (E), and 5.94 (EC); P<0.05 (C, S, R, vs. T, E, EC; T vs. E; EC vs. T, E). CONCLUSION: Our study showed a decrease in the extent of aortic atherosclerosis in oophorectomized cholesterol-fed rabbits treated with tibolone or estradiol, and a decrease in aortic cholesterol content in rabbits treated with tibolone, raloxifene and estradiol. However, rabbits treated with tibolone showed an increased uterine weight, which is contrary to that observed in humans. |
| Effects of estrogen and progesterone on plasma platelet-activating factor-acetylhydrolase activity and low-density lipoprotein cholesterol concentration in men Ohshige, A., M. Ito, et al. (1996), Artery 22(3): 115-24. Abstract: OBJECTIVE: We examined the effects of estrogen and progesterone on the plasma platelet-activating factor (PAF)-acetylhydrolase activity and lipoprotein concentrations in men. METHOD: Ten healthy men received 6 days of oral mestranol (0.24 mg/day) followed by 6 days of oral norethisterone (20 mg/day). The PAF-acetylhydrolase activity and lipoprotein profiles were determined in each subject prior to and following mestranol loading and following norethisterone administration. RESULT: The mestranol caused a significant decrease in both the plasma PAF-acetylhydrolase activity and the low-density lipoprotein (LDL) cholesterol concentrations of 26.4% and 26.9%, respectively; norethisterone appeared to revert the PAF-acetylhydrolase activity and LDL cholesterol concentrations to the levels observed prior to mestranol loading. In addition, the plasma PAF-acetylhydrolase activity was positive correlated with the LDL cholesterol concentration (r = 0.58, P < 0.001). CONCLUSION: The results of this study indicate that mestranol and norethisterone exert an effect on the plasma PAF-acetylhydrolase activity in men, possibly by influencing plasma LDL cholesterol concentrations. |
| Effects of estrogen on atherosclerosis formation and serum nitrite/nitrate concentrations in cholesterol-fed ovariectomized rabbits Akishita, M., K. Kozaki, et al. (1996), J Atheroscler Thromb 3(2): 114-9. Abstract: This study was to examine the effects of estrogen replacement on atherosclerosis formation in ovariectomized cholesterol-fed rabbits. We also examined serum levels of nitrite/nitrate, stable metabolites of nitric oxide, to investigate the involvement of nitric oxide. Female New Zealand White rabbits were ovariectomized and divided into 3 groups; 1) fed a normal diet (ND group, n=5), 2) fed a 1% cholesterol diet (CD group, n=6), or 3) fed a 1% cholesterol diet and received estrogen replacement (CD+E group, n=7). After 3 months, the rabbits were sacrificed to examine atherosclerosis formation. Atherosclerosis was not observed in ND. The oil red 0 positive area in the aorta was significantly greater in CD than in CD+E (CD, 17.3+/-2.2; CD+E, 9.3+/-0.8%, p<0.05). Stenosis of the coronary artery was also significantly greater in CD than in CD+E (CD, 30.6+/-9.7; CD+E, 6.7+/-2.9%, p <0.05). There was no significant difference in serum lipids between CD and CD+E. Serum nitrite/nitrate levels were significantly lower in CD than in ND (ND, 37.6+/-3.6; CD, 25.3+/-3.1 microM, p<0.05). There was a non-significant trend towards higher nitrite/nitrate levels after estrogen replacement (CD+E, 34.4+/-3.8 microM, p=0.08 vs. CD). These results suggest that direct actions on vascular wall including nitric oxide production contribute to the anti-atherogenic effects of estrogen. |
| Effects of ethanol on lipid bilayers containing cholesterol, gangliosides, and sphingomyelin Barry, J. A. and K. Gawrisch (1995), Biochemistry 34(27): 8852-60. Abstract: The influence of lipid composition on the response of bilayers to ethanol binding was investigated with 2H NMR spectroscopy. The bilayers were composed of various combinations of the lipids most often found in neural cell membranes: phosphatidylcholines (PCs), gangliosides, sphingomyelin, and cholesterol. The PCs, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), were chain-perdeuterated to allow the response of bilayer order to ethanol to be monitored at all positions through the depth of the bilayer interior. All bilayers were investigated in the lamellar liquid-crystalline (L alpha) phase. The results from the de-Paked NMR spectra demonstrate that ethanol binding in the lipid-water interface Barry, J. A., & Gawrisch, K. (1994) Biochemistry 33, 8082-8088 alters order parameter profiles in the bilayer interior differently for the various lipid mixtures. The presence of 10 mol % brain gangliosides enhanced the disordering effect of ethanol and altered the response of the order profile along the PC chains. This effect was apparently caused by sugar-ethanol interactions in the oligosaccharide head group. The impact of the ceramide moiety of brain sphingomyelin (50 mol % in DMPC) was negligible. In bilayers containing cholesterol, the binding of ethanol and its effects on the hydrocarbon interior were found to reflect the phase transition to the liquid-ordered phase at about 25 mol % cholesterol Thewalt, J. L., & Bloom, M. (1992) Biophys. J. 63, 1176-1181. Results from the quadrupolar splittings for deuterated ethanol (CH3CD2OH) bound to cholesterol-containing bilayers showed that ethanol binding decreased with increasing amounts of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effects of ethanol on lipid bilayers with and without cholesterol: the distearoylphosphatidylcholine system Tran, R., S. Ho, et al. (2004), Biophys Chem 110(1-2): 39-47. Abstract: Differential scanning calorimetry (DSC) and fluorescence spectroscopy are useful techniques for investigating the phase transitions of phospholipid bilayers. In this study, these methods have been extended to determine the effects of ethanol on DSPC and DSPC/2 mol.% cholesterol bilayers. The biphasic effect of the main transition was observed on the DSC heating scans above 0.60 M ethanol. In addition, the concentration at which the biphasic effect occurs is not significantly changed in the presence of 2 mol.% cholesterol. For the fluorescence studies, 1,6-diphenyl-1,3,5-hexatriene (DPH) has been incorporated into the bilayer to monitor the phase transitions through the displacement of DPH. This fluorescent probe is used to directly determine the onset of interdigitation in the bilayer systems as indicated by a large decrease in the DPH fluorescence intensity. The addition of cholesterol lowered and broadened the transition temperatures of the phosphatidylcholine (PC) system. However, 2 mol.% cholesterol did not have a significant effect on the induction of the interdigitated phase in DSPC as observed from the small difference in ethanol threshold concentration for the two systems. This suggests that DSPC forms a more stable interdigitated gel phase than other PCs with shorter acyl chains. |
| Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on elasticity and endothelium-dependent relaxation of the aorta in high cholesterol diet-fed rabbits Sato, M., Y. Katsuki, et al. (1994), Nippon Yakurigaku Zasshi 104(1): 31-8. Abstract: We studied the elasticity and endothelium-dependent relaxation (EDR) of the aorta in 1% cholesterol diet (HCD)-fed rabbits. Furthermore, the effects of ethyl all-cis-5,8,11,14, 17-icosapentaenoate (EPA-E) were examined in this model of atherosclerosis. After 12 weeks of feeding with HCD, the animals showed increase in plasma total cholesterol level, formation of atherosclerotic plaque, decrease in aortic elasticity and impairment of EDR to acetylcholine (ACh). The levels of aortic elasticity in HCD-fed rabbits administered orally with EPA-E (300 mg/kg for 12 weeks) were almost the same as those of rabbits fed a normal diet, although EPA-E showed no effects on the plasma total cholesterol level and formation of atherosclerotic plaque in HCD-fed rabbits. On EDR in response to ACh and cyclic GMP formation in the HCD-fed rabbit aorta, EPA-E improved the impairment of these parameters, but not significantly. Therefore, EPA-E had little effect on the endothelium in this model of atherosclerosis, although EPA-E improved the decrease in the aortic elasticity. Because the levels of aortic elasticity showed no significant correlation with the magnitude of EDR to ACh or the size of atherosclerotic plaque, the decrease of aortic elasticity in this model of atherosclerosis was thought to have little relation to the dysfunction of the endothelium. |
| Effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate on the physical properties of arterial walls in high cholesterol diet-fed rabbits Sato, M., Y. Katsuki, et al. (1993), J Cardiovasc Pharmacol 22(1): 1-9. Abstract: The effects of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on in vivo physical properties of arteriosclerotic aorta and femoral artery in high cholesterol diet (HCD)-fed rabbits were studied. The aortic pulse wave velocity (PWV) of rabbits fed HCD for 12 weeks (control group) tended to be higher than that of rabbits fed a normal diet (normal group). Because the PWVs in HCD-fed rabbits administered orally with 30 and 300 mg/kg/day EPA-E were significantly lower than the PWV of the control group, the distensibility of arteriosclerotic aorta was improved with administration of EPA-E. The stiffness parameter (beta) value as an in vivo indicator of arteriosclerosis was significantly higher in the control group than in the normal group and improved with administration of EPA-E to almost the same level as that of the normal group. The beta-values were in significant negative correlation with medial elastin content and medial smooth muscle cell (SMC) density in thoracic aorta and in positive correlation with the free cholesterol content in abdominal aortic SMC. On the other hand, they were not correlated with either the cross-sectional area of intimal thickening lesions or the plasma lipid levels measured simultaneously. The femoral PWVs were, like those in the aorta, higher in the control group as compared with the normal group, and the changes were improved with administration of EPA-E. These results show that EPA-E improved the in vivo distensibility of arteriosclerotic arteries in HCD-fed rabbits.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Effects of excess dietary tyrosine on cholesterol, bile acid metabolism and mixed-function oxidase system in rats Nagaoka, S., H. Miyazaki, et al. (1990), J Nutr 120(10): 1134-9. Abstract: Excess dietary tyrosine (12%) caused hypercholesterolemia in male Wistar rats and significantly increased cytochrome P-450 and b5 contents. Bile flow and biliary output of total bile acids were significantly increased in rats fed this diet. Biliary output of cholesterol was not significantly altered, whereas that of taurocholic acid was significantly increased. Excess dietary tyrosine significantly decreased the fecal excretion of neutral steroids, whereas total steroid excretion was not significantly changed. The present results indicate that excess dietary tyrosine causes hypercholesterolemia without modifying the fecal total steroid excretion, thus supporting our previous hypothesis that stimulated synthesis of cholesterol is a main reason why excess dietary tyrosine leads to hypercholesterolemia. |
| Effects of exercise with varying energy expenditure on high-density lipoprotein-cholesterol Visich, P. S., F. L. Goss, et al. (1996), Eur J Appl Physiol Occup Physiol 72(3): 242-48. Abstract: To investigate the effect of varying energy expenditure on acute high-density lipoprotein-cholesterol (HDL-C) changes, 12 healthy endurance-trained men completed three- counterbalanced running trials at different energy expenditures: trial 1, 1690.3 (24.4) kJ mean (SD); trial 2, 2529.1 (24.0) kJ; trial 3, 3384.3 (36.6) kJ, with exercise intensity at 75% of maximal oxygen consumption. For each trial, blood samples were collected at 24 h pre-exercise (24 h Pre), immediately post-exercise, 1 h post-exercise, 6 h post-exercise (6 h PE), and 24 h post-exercise (24 h PE). Plasma samples were analyzed for HDL-C, HDL2-C and HDL3-C subfractions, and triglycerides (TG). In addition, post-heparin plasma samples were analyzed at 24 h Pre, 6 h PE and 24 h PE for lipoprotein lipase activity (LPLA) and hepatic triglyceride lipase activity. All samples were corrected for plasma volume changes and compared to 24 h Pre (baseline). When trials were combined, an increase (P < 0.05) in HDL-C was observed 24 h PE, via an increase (P < 0.05) in HDL3-C. An increase (P < 0.05) in LPLA and decrease (P < 0.05) in TG at 24 h PE is suggested to be responsible for the increase in HDL3-C. In conclusion, no difference in HDL-C was observed among trials. However, when trials were combined, an increase in HDL-C was observed, suggesting that an energy expenditure of no greater than 3384 kJ is needed to promote favorable changes in HDL-C. |
| Effects of exercise, dietary cholesterol, and dietary fat on blood lipids Johnson, C. and P. Greenland (1990), Arch Intern Med 150(1): 137-41. Abstract: Exercise, a low fat diet, or a diet low in saturated fat content can each lower plasma total cholesterol and low-density lipoprotein (LDL) cholesterol. We investigated whether these factors together could prevent the lipid-raising effects of dietary cholesterol. Ten healthy, athletic, normolipidemic male volunteers were studied. Two diets of 4 weeks duration each were compared in a randomized, blind crossover design. Diets were identical except for cholesterol content: one contained 600 mg/d; the other 200 mg/d. Both diets contained 15% of calories as protein, 55% as carbohydrate, 30% as fat, and the polyunsaturated fat to saturated fat ratio was 1.5. Exercise level and body weight were kept constant in each subject. As compared with plasma values obtained following the 200-mg/d cholesterol diet, mean values following the 600-mg/d cholesterol diet significantly increased for LDL cholesterol and apolipoprotein B by 10% and 13%, respectively. Mean plasma triglycerides, high-density lipoprotein 2 and 3, and apolipoprotein A-1 levels did not change significantly. Individual responses, however, were highly variable. Three subjects increased LDL cholesterol by more than 25%; 2 subjects increased LDL cholesterol by 10% to 25%; and 5 subjects had 5% or less change in LDL cholesterol. A dietary cholesterol increase can significantly elevate plasma LDL cholesterol and apolipoprotein B in certain normolipidemic, healthy men even when they are exercising regularly and consuming a moderately fat restricted, low saturated fat diet. Dietary cholesterol restriction may therefore be justifiable even when other life-style and dietary measures to minimize blood cholesterol are undertaken. |
| Effects of exogenous apo E-3 and of cholesterol-enriched meals on the cellular metabolism of human chylomicrons and their remnants Arnon, R., E. Sehayek, et al. (1991), Biochim Biophys Acta 1085(3): 336-42. Abstract: The effects of exogenous apo E-3 and of cholesterol-enriched meals on the binding, cell association and proteolytic degradation of human chylomicrons and their remnants were determined in cultured human skin fibroblasts. Chylomicrons were prepared from plasma of normolipemic humans 4 h after a fat meal with normal or high cholesterol content. Remnants were obtained after incubation of chylomicrons with lipoprotein lipase in vitro. Cellular metabolism of chylomicrons was minimal, less than 10% that of LDL. Exogenous apo E-2 enhanced chylomicron metabolism by 3-4-fold. The cellular metabolism of remnants was 2.5-3.5-fold higher as compared to intact chylomicrons but their response to exogenous apo E-3 was considerably lower. The cellular metabolism of chylomicrons and chylomicron remnants obtained from subjects eating cholesterol-enriched fat meal was the highest either without or with added exogenous apo E-3. Yet, even in the preparation that exhibits the highest metabolic activity (apo E-3 enriched remnants from cholesterol-enriched meals) the absolute proteolytic degradation was about two-thirds that of LDL. We conclude that although LDL-receptors take up and degrade chylomicron remnants, the rate of catabolism of remnants by this route can not explain the rapid and complete remnant removal process as observed in vivo. |
| Effects of exogenous fatty acids and cholesterol on aminopeptidase activities in rat astroglia Ramirez-Exposito, M. J., M. J. Garcia, et al. (2002), Cell Biochem Funct 20(4): 285-90. Abstract: Several studies have addressed the interaction between fatty acids and lipids with central nervous system peptides. Because aminopeptidases (AP) are involved in the regulation of neuropeptides, this work studies several AP expressed in cultured astroglia, after exogenous addition of oleic and linoleic fatty acids and cholesterol to the culture medium. Alanyl-AP, arginyl-AP, cystyl-AP, leucyl-AP, tyrosyl-AP and pyroglutamyl-AP activities were analysed in whole cells using the corresponding aminoacyl-beta-naphthylamides as substrates. Oleic acid inhibits alanyl-AP, cystyl-AP and leucyl-AP activities, whereas linoleic acid inhibits alanyl-AP, arginyl-AP and tyrosyl-AP activities. Neither oleic acid nor linoleic acid modifies pyroglutamyl-AP activity. In contrast, cholesterol increases arginyl-AP, cystyl-AP, leucyl-AP, tyrosyl-AP and pyroglutamyl-AP activities, although it does not modify alanyl-AP activity. The changes reported here suggest that oleic and linoleic fatty acids and cholesterol can modulate peptide activities via their degradation route involving aminopeptidases; each of them being differentially regulated. |
| Effects of exposure to carbon disulphide on low density lipoprotein cholesterol concentration and diastolic blood pressure Egeland, G. M., G. A. Burkhart, et al. (1992), Br J Ind Med 49(4): 287-93. Abstract: The relation of carbon disulphide (CS2) exposure to risk factors for ischaemic heart disease was recently examined using data from a 1979 cross sectional study of 410 male textile workers, of whom 165 were exposed and 245 were unexposed to CS2. Average eight hour CS2 exposure concentrations ranged from 0.6 to 11.8 ppm by job title category among the exposed workers. A significant and positive linear trend in low density lipoprotein cholesterol concentration (LDLc) and diastolic blood pressure with increasing CS2 exposure was found after adjustment for potential confounders. When exposure was examined as a categorical variable (none, low, moderate, and high), the high exposure group had an adjusted mean LDLc that was 0.32 mmol/l greater than the non-exposed group (p = 0.02), and an adjusted mean diastolic blood pressure that was 3.16 mm Hg greater than the non-exposed group (p = 0.09). The effect of CS2 on diastolic blood pressure was strengthened in analyses limited to exposed workers: the high exposure group had an adjusted mean diastolic blood pressure that was 5 mm Hg greater than that of the low exposed group (p = 0.03). Triglyceride, high density lipoprotein cholesterol, and fasting glucose concentration, and systolic blood pressure were not affected by exposure. Blood lead concentration was positively associated with systolic and diastolic blood pressure. The results indicate that relatively modest exposure to CS2 may raise LDLc concentration and diastolic blood pressure and suggest mechanisms by which exposure to CS2 may influence risk of ischaemic heart disease. Also the results provide further support for the hypothesis of a possible association between blood lead concentration and blood pressure. |
| Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia Knopp, R. H., H. Gitter, et al. (2003), Eur Heart J 24(8): 729-41. Abstract: AIMS: This randomized, double-blind, placebo-controlled, parallel-group study evaluated the safety and efficacy of ezetimibe 10 mg/day in patients with primary hypercholesterolemia. METHODS AND RESULTS: Following dietary stabilization, a 2-12-week washout period, and a 4-week, single-blind, placebo lead-in period, 827 patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =3.36 mmol/l (130 mg/dl) to < or =6.47 mmol/l (250 mg/dl) and triglycerides < or =3.95 mmol/l (350 mg/dl) were randomized 3:1 to receive ezetimibe 10 mg or placebo orally once daily in the morning for 12 weeks. The primary efficacy endpoint was percentage reduction in direct plasma LDL-C. Ezetimibe reduced direct LDL-C by a mean of 17.7% from baseline to endpoint, compared with an increase of 0.8% with placebo (P<0.01). Response to ezetimibe was generally consistent across all subgroups analyzed. Ezetimibe also significantly improved levels of plasma total cholesterol, apolipoprotein B, high-density lipoprotein(2)-cholesterol and lipoprotein(a), and elicited a trend toward lower triglyceride levels. Ezetimibe did not alter the serum concentrations of lipid-soluble vitamins or significantly affect baseline or stimulated cortisol production. Ezetimibe was well tolerated, with a safety profile similar to that of placebo. CONCLUSIONS: Ezetimibe, which significantly reduces LDL-C and favorably affects other lipid variables, may provide a well tolerated and effective new option for lipid management in the future. |
| Effects of F2833 on cholesterol metabolism in the genetically hyperlipidemic rat Ouguerram, K., C. Lutton, et al. (2001), Eur J Pharmacol 415(2-3): 293-9. Abstract: The effects of the new hypolipidemic agent, F2833 or (chloro 2' (1-1') biphenyl-4)-2 propanol-2, on cholesterol metabolism were studied in genetically hyperlipidemic rats (RICO). Cholesterolemia decreased after 2 days of treatment to 60% of its initial value (1.20+/-0.10 g/l vs. 1.99+/-0.08, P < 0.001) and then stabilised within 10 days. This hypocholesterolemic action was effective for as long as 3 months. Concerning the different classes of lipoproteins, a significant drop was observed in HDL (high density lipoproteins) (25%, 0.49 +/- 0.02 g/l vs. 0.66 +/- 0.007, P < 0.01) and particularly in LDL (low density lipoproteins) (70%, 0.30 +/- 0.04 g/l vs. 0.92 +/- 0.05, P < 0.001). Whole body cholesterol showed a higher fractional catabolic rate (0.25 +/- 0.02 vs. 0.17 +/- 0.005 day(-1), P < 0.01) together with an increased cholesterol synthesis (60 +/- 5 vs. 36 +/- 4 mg/day, P < 0.01). LDL kinetics showed that the decrease in these lipoproteins is essentially caused by an increase in the fractional catabolic rate (10.6 +/-0.1%/h vs. 5.2 +/- 0.1%/h, P < 0.001) and by a lesser decrease in the LDL production rate. This cholesterol metabolic profile created by treatment suggests an effect through stimulation of cholesterol output (biliary cholesterol elimination or cholesterol transformation into bile acids). |