| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Incorporation of cholesterol into the cellular membrane of Bifidobacterium longum Dambekodi, P. C. and S. E. Gilliland (1998), J Dairy Sci 81(7): 1818-24. Abstract: Four strains of Bifidobacterium longum were isolated from feces of human intestinal sources and were tested along with four commercially available strains of B. longum for bile tolerance, the ability to deconjugate sodium taurocholate, and the ability to remove cholesterol from the culture medium. The cultures varied with respect to each test. There was no relationship between bile tolerance and the ability to remove cholesterol. Relative deconjugation of sodium taurocholate also was not related directly to the amount of cholesterol that was removed by the cultures. However, inclusion of sodium taurocholate in the growth medium enhanced the ability of B. longum to remove cholesterol from the medium during growth. A portion of the cholesterol that was removed from the growth medium by B. longum was recovered in the cellular membrane fraction, suggesting some assimilation of cholesterol into the membrane. Cells that were grown in the presence of cholesterol and taurocholate were more resistant to sonication than were those grown in the control broth or in the broth containing the bile salt without cholesterol, which is evidence that the cell envelope was affected by the cholesterol. |
| Incorporation of cholesterol into the cellular membrane of Lactobacillus acidophilus ATCC 43121 Noh, D. O., S. H. Kim, et al. (1997), J Dairy Sci 80(12): 3107-13. Abstract: Cholesterol that was assimilated by Lactobacillus acidophilus ATCC 43121 was not metabolically degraded; most of it was recovered with the cells. Cells that were grown in the presence of cholesterol micelles and bile salts were more resistant to lysis by sonication than were those grown in their absence, suggesting a possible alteration of the cell wall or membrane. Cholesterol assimilation occurred during growth at pH 6.0 as well as during growth without pH control. Part of the cholesterol that was assimilated by cells was recovered in the membrane fractions of cells grown under both conditions. There was no difference in the amount taken up from cholesterol micelles that were prepared using dioleoyl L-alpha-phosphatidylcholine or distearoyl L-alpha-phosphatidylcholine. Thus, the type of fatty acid (unsaturated or saturated) in the phospholipid did not influence the assimilation. As the amount of Tween 80 in the growth media increased beyond 0.05%, cholesterol uptake decreased, and the amount of growth remained the same. The higher concentrations of Tween 80 may have adversely affected the permeability of the cells. |
| Incorporation of cholesterol oxidation products into cell lipids and their influence on the proliferation of cultured cardiomyocytes Bordoni, A., S. Hrelia, et al. (1995), Cardioscience 6(2): 107-13. Abstract: We have investigated the incorporation of cholesterol oxidation products into cardiomyocyte lipids and related this to changes in cell proliferation, evaluated by measuring cellular protein content. Primary cultures of neonatal rat ventricular cells were supplemented with scalar concentrations of several cholesterol oxidation products (cholestan-5 alpha, 6 alpha-epoxy-3 beta-ol, 5 alpha-cholestane-3 beta, 5, 6 beta-triol, 5-cholesten-3 beta, 4 beta-diol, 5-cholesten-3 beta-ol-7-one, and 5-cholesten-3-one). Although all the cholesterol oxidation products were incorporated into the cardiomyocyte lipids when added to the medium at a concentration higher than 0.5 microM, the extent of the incorporation of the different cholesterol oxidation products differed, depending on the concentration in the culture medium and on the chemical structure of the compound. The effects of the cholesterol oxidation products on the cellular protein content were also different: 5 alpha-cholestane-3 beta, 5, 6 beta-triol was shown to be the most potent inhibitor of cell proliferation, followed by cholestan-5 alpha, 6 alpha-epoxy-3 beta-ol, 5-cholesten-3 beta, 4 beta-diol and 5-cholesten-3 beta-ol-7-one. 5-Cholesten-3-one did not affect the cellular protein content. The ability of cholesterol oxidation products to inhibit cell proliferation, and their capacity to increase the permeability of the plasma membrane to calcium, could be deleterious for cardiac cells. |
| Incorporation of lean red meat into a National Cholesterol Education Program Step I diet: a long-term, randomized clinical trial in free-living persons with hypercholesterolemia Hunninghake, D. B., K. C. Maki, et al. (2000), J Am Coll Nutr 19(3): 351-60. Abstract: OBJECTIVE: Clinicians often recommend that intake of all meat, particularly red meat, be reduced in conjunction with a low-fat, low-cholesterol diet to reduce low-density lipoprotein (LDL) cholesterol. This study was designed to determine the long-term effects of lean red meat (beef, veal and pork) compared to lean white meat (poultry and fish) consumption on lipoprotein concentrations in free-living hypercholesterolemic subjects consuming a National Cholesterol Education Program (NCEP) Step I diet. METHODS: A randomized, crossover design was utilized. Hypercholesterolemic men and women (LDL cholesterol between 3.37 and 4.92 mmol/L) (triglycerides <3.96 mmol/L) (n = 145) were counseled to consume > or =80% of their 170 g/d meat intake as either lean red meat or lean white meat for two 36-week phases, separated by a four-week washout period of free meat selection. Subjects were instructed to follow an NCEP Step I diet throughout the study. RESULTS: There were no significant differences in lipid concentrations between the lean red meat and lean white meat phases. LDL cholesterol was 4.02+/-0.04 (SEM) and 4.01+/-0.04 mmol/L in the white and red phases, respectively; this represented a decrease of approximately 2% from baseline concentrations (p < 0.01). Total cholesterol also declined by 1% from baseline (p < 0.05), and high-density lipoprotein (HDL) cholesterol rose over the study period by approximately 2% to approximately 3% from baseline to reach concentrations of 1.37+/-0.03 mmol/L and 1.38+/-0.03 mmol/L in the white and red phases, respectively (p < 0.001). Triglycerides were not altered by treatment. CONCLUSIONS: Consumption of lean red meat or lean white meat, as part of an NCEP Step I diet, is similarly effective for reducing LDL cholesterol and elevating HDL cholesterol concentrations in free-living persons with hypercholesterolemia. |
| Incorporation of MAL, an integral protein element of the machinery for the glycolipid and cholesterol-mediated apical pathway of transport, into artificial membranes requires neither of these lipid species Puertollano, R., M. Menendez, et al. (1999), Biochem Biophys Res Commun 266(2): 330-3. Abstract: The MAL proteolipid, an integral membrane protein with selective residence in glycolipid- and cholesterol-enriched membrane (GEM) microdomains, has recently been identified as being an element of the integral protein machinery necessary for apical transport in MDCK cells. With the use of a recombinant baculovirus, we have expressed and purified polyhistidine-tagged MAL to determine whether MAL has special lipid requirements for becoming incorporated into membranes. In contrast with caveolin-1, a component of GEMs that requires cholesterol for its integration into artificial membranes, MAL incorporation took place with dimyristoylphosphatidylcholine as the only lipid component. The presence of cholesterol, sphingomyelin, or galactocerebrosides did not affect the efficiency of this process. These results indicated that MAL is compatible with membranes containing either only phospholipids or also glycolipids and cholesterol and are consistent with the reported requirement of a sorting event for the specific targeting of MAL to GEM microdomains. |
| Incorporation of medium chain triacylglycerols into phospholipid bilayers: effect of long chain triacylglycerols, cholesterol, and cholesteryl esters Hamilton, J. A., J. M. Vural, et al. (1996), J Lipid Res 37(4): 773-82. Abstract: The ability of water-insoluble molecules such as triacylglycerols to partition from oil phases into phospholipid interfaces may be crucial to their hydrolysis by lipases in the aqueous environment of plasma and cells. This study uses high resolution and magic angle spinning 13C NMR spectros-copy to measure the solubility of the 8-carbon medium chain triacylglycerol, trioctanoin, in the lamellar structure of phospholipids (vesicles and multilayers) in the presence of other neutral lipids that may compete for an interfacial location (long chain triacylglycerol, cholesteryl ester, and cholesterol). In the presence of a saturating concentration of triolein (approximately 3 mole%), the solubility of trioctanoin in egg phosphatidylcholine vesicles decreased from 10 mole% to 7 mole%. The presence of a saturating concentration of trioctanoin (approximately 10 mole%) decreased the interfacial solubility of long chain triolein to approximately 1 mole%. Cholesteryl oleate in phospholipid vesicles slightly diminished the incorporation of trioctanoin into the surface. The presence of cholesterol reduced the interfacial solubility of trioctanoin, but at a high level of cholesterol (30 mole%), trioctanoin had a solubility of 3 mole%. Thus, even in the presence of other competing neutral lipids, medium chain triacylglycerol retains a favorable location and surface concentration for efficient hydrolysis. 13C NMR analysis thus provides an explanation for preferential hydrolysis of medium, compared to long chain triacylglycerol, in a physical blend of medium and long chain triacylglycerol in a single emulsion particle, and in general, a valuable approach to determine substrate availability at phospholipid surfaces. |
| Incorporation of steroidogenic pathways which produce cortisol and aldosterone from cholesterol into nonsteroidogenic cells Mathew, P. A., J. I. Mason, et al. (1990), Mol Cell Endocrinol 73(1): 73-80. Abstract: Cortisol production from cholesterol requires the activity of four steroid hydroxylases: cholesterol side chain cleavage cytochrome P-450 (P-450scc), 17 alpha-hydroxylase cytochrome P-450 (P-45017 alpha), 21-hydroxylase cytochrome P-450 (P-450C21) and 11 beta-hydroxylase cytochrome P-450 (P-45011 beta). We have previously shown that transformed, nonsteroidogenic COS 1 cells derived from monkey kidney are a useful system for expression of various forms of cytochrome P-450. The present study shows that COS 1 cell cultures multiply transfected with six plasmids containing all four steroid hydroxylases, 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase (3 beta HSD) and adrenodoxin produce cortisol and aldosterone when 22(R)-hydroxycholesterol is supplied to the system. When pregnenolone is used as substrate, various intermediate metabolites are detected at different time points further establishing the incorporation of complete functional steroidogenic pathways into the nonsteroidogenic cell cultures. Since the first and the last reactions in these pathways take place in the mitochondrion, the movement of various intermediate metabolites from mitochondrion to endoplasmic reticulum and back to mitochondrion occurs in and between COS 1 cells. |
| Increase in cholesterol and cholesterol oxidation products, and role of cholesterol oxidation products in kainate-induced neuronal injury Ong, W. Y., E. W. Goh, et al. (2003), Brain Pathol 13(3): 250-62. Abstract: Little is known about changes in sterols, in particular cholesterol, and cholesterol oxidation products (COPs) in oxidative injury in neural tissues. We have therefore examined changes in cholesterol and COPs using a model of excitotoxic injury. Intracerebroventricular injections of kainate in rats resulted in an increase in immunoreactivity to cholesterol in the affected CA fields of the hippocampus. The increase was confirmed by increased filipin staining of cholesterol in adjacent sections from the same animals, and in hippocampal slice or neuronal cultures after kainate treatment. In neuronal cultures, addition of lovastatin, an inhibitor of cholesterol synthesis, attenuated the increased filipin staining after kainate treatment, indicating that the increase in cholesterol could involve increased cholesterol synthesis. Furthermore, gas chromatographic mass spectrometric (GC/MS) analysis of cholesterol and COPs in kainate-injected rat brain showed a marked increase in cholesterol and COPs including 7-ketocholesterol, 3 days after kainate treatment. The addition of some COPs, including 7-ketocholesterol and cholesterol epoxides to hippocampal slices resulted in neuronal injury as reflected by decreased staining of a neuronal marker in the affected CA fields. The ability of these COPs to produce neuronal injury was attenuated by glutathione, suggesting that oxidative mechanisms are involved in neuronal injury induced by these products. These results, together with GC/MS results that showed significant increase in 7-ketocholesterol at 3 days post-kainate injury suggest that 7-ketocholesterol may be a factor in aggravating oxidative damage to neurons, after the initial stages of kainate-induced neuronal injury. |
| Increase in plasma total and lipoprotein cholesterol during incubation of whole blood samples at 37 degrees C--influence of LCAT inhibitors Ruhling, K., A. Lang, et al. (1992), Clin Chim Acta 205(3): 205-12. Abstract: Incubation of whole blood samples at 37 degrees C caused a time-dependent increase in plasma cholesterol concentrations. In samples from 40 fasting healthy males, plasma cholesterol rose by 13.6 +/- 3% during 24 h (P less than 0.001). Changes in cholesterol concentrations were found in both the HDL fraction and the VLDL/LDL fraction. The increase in lipoprotein cholesterol concentrations correlated positively with the initial levels of HDL cholesterol and apo A-I; and with the original levels of VLDL/LDL cholesterol, apo B and triglycerides. The increase in plasma total cholesterol was not related to the HDL cholesterol and apo A-I concentrations. It was more pronounced in samples with elevated plasma concentrations of total cholesterol, VLDL/LDL cholesterol, apo B and triglycerides. The elevation in plasma total cholesterol resulted from an increase in cholesteryl esters, whereas free cholesterol decreased. After LCAT inhibition no changes in total, free and esterified cholesterol were observed. Therefore, increase in plasma cholesterol seems to represent a LCAT-dependent cholesterol transport out of blood cells. |
| Increase in pulse pressure relates to diabetes mellitus and low HDL cholesterol, but not to hyperlipidemia in hypertensive patients aged 50 years or older Miyagi, T., H. Muratani, et al. (2002), Hypertens Res 25(3): 335-41. Abstract: Higher pulse pressure is associated with higher cardiovascular risk. We investigated the relationship between pulse pressure and known metabolic risk factors in hypertensive patients who had not experienced stroke or myocardial infarction. In a multicenter cross-sectional survey made in 1995, we registered 939 hypertensive patients aged > or = 50 years. Of these, 734 had never experienced stroke or myocardial infarction. We divided these 734 patients into two groups based on the value of their pulse pressures: 396 patients with a pulse pressure > or = 60 mmHg, and 338 patients with a pulse pressure<60 mmHg. The average pulse pressure value was 72 +/- 12 mmHg in the former group, and 49 +/- 8 mmHg in the latter group. The former group exhibited advanced age, a higher women-to-men ratio, lower high-density lipoprotein (HDL) cholesterol, and higher systolic and lower diastolic blood pressure. Diabetes mellitus (DM) and left ventricular hypertrophy were more frequently noticed in the former group than in the latter group. The prevalence of hyperlipidemia, however, was similar in the two groups. The association of pulse pressure with DM and low HDL cholesterol was statistically significant by multiple logistic analysis adjusted for age, sex, and other known cardiovascular risk factors. In conclusion, pulse pressure increases with advancing age. DM made a substantially larger contribution to the increase in pulse pressure than hyperlipidemia. |
| Increase in serum amyloid a evoked by dietary cholesterol is associated with increased atherosclerosis in mice Lewis, K. E., E. A. Kirk, et al. (2004), Circulation 110(5): 540-5. Abstract: BACKGROUND: Elevated serum amyloid A (SAA) levels are associated with increased cardiovascular risk. SAA levels can be increased by dietary fat and cholesterol. Moreover, SAA can cause lipoproteins to bind extracellular vascular proteoglycans, a process that is critical in atherogenesis. Therefore, we hypothesized that diet-induced increases in SAA would increase atherosclerosis independent of their effect on plasma cholesterol levels. METHODS AND RESULTS: Female LDL-receptor-null (LDLR-/-) mice were fed high-saturated fat diets (21%, wt/wt), with or without added cholesterol (0.15%, wt/wt), for 10 weeks. Compared with chow-fed controls, the high-fat diets increased plasma SAA levels. Addition of cholesterol further increased SAA levels 2-fold (P<0.05) without further increasing plasma cholesterol levels. Addition of dietary cholesterol also increased atherosclerosis (P<0.05). Four lines of evidence suggest that SAA actually might cause atherosclerosis: (1) SAA levels when mice were euthanized correlated with the extent of atherosclerosis (r=0.49; P<0.02); (2) SAA levels after 5 weeks of diet correlated with the extent of atherosclerosis at 10 weeks (r=0.66; P<0.01); (3) binding of HDL from these animals to proteoglycans in vitro was related to the HDL-SAA content (r=0.65; P<0.01); and (4) immunoreactive SAA was present in lesion areas enriched with both proteoglycans and apolipoprotein A-I, the major HDL apolipoprotein. CONCLUSIONS: Addition of cholesterol to a high-fat diet increased plasma SAA levels and atherosclerosis independent of an adverse effect on plasma lipoproteins, consistent with the hypothesis that SAA may promote atherosclerosis directly by mediating retention of SAA-enriched HDL to vascular proteoglycans. |
| Increase in serum and bile cholesterol and HMG-CoA reductase by lovastatin in rats Yamauchi, S., W. G. Linscheer, et al. (1991), Am J Physiol 260(4 Pt 1): G625-30. Abstract: Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, is effective in the treatment of hypercholesterolemic patients and is currently being evaluated as a potential agent for dissolving gallstones. We therefore evaluated its effect on cholesterol metabolism in a rat model. A low-cholesterol diet containing 0.1% lovastatin was fed 15 h and 7 and 21 days. Microsomal HMG-CoA reductase activity, hepatic cholesterol synthesis, blood cholesterol, and biliary lipid output were determined and compared with control rats. Hepatic cholesterol synthesis increased ninefold after 7 days and levels of HMG-CoA reductase activity sevenfold. Biliary cholesterol excretion maximally increased fourfold. Biliary lipid output was still elevated after 21 days of treatment (cholesterol 3-fold and phospholipid 2-fold, P less than 0.01). Bile salt output did not change. Augmented responses to lovastatin were present but less on the high-cholesterol diet. The data are consistent with the hypothesis that lovastatin increases HMG-CoA reductase activity through a feedback mechanism that promoted increased cholesterol synthesis, biliary lipid secretion, and elevated blood cholesterol. There was an apparent coupling of biliary cholesterol output with phospholipids but not with bile salts. Although lovastatin also increased microsomal HMG-CoA reductase activity in humans, cholesterol synthesis is not stimulated but is inhibited. This may be explained by higher permeability of the microsomal membranes for lovastatin. Thus the effect of HMG-CoA reductase inhibitors on cholesterol synthesis in different species should then depend on the properties of microsomal membranes. |
| Increase in the active form of 3-hydroxy-3-methylglutaryl coenzyme A reductase in human hepatocellular carcinoma: possible mechanism for alteration of cholesterol biosynthesis Kawata, S., K. Takaishi, et al. (1990), Cancer Res 50(11): 3270-3. Abstract: 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity and the rate of sterol biosynthesis are positively correlated with DNA synthesis and proliferation of mammalian cells. The total (active plus latent) activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and the activity of its active form in hepatocellular carcinoma (HCC) from seven patients were measured and compared with those in liver tissue from five control subjects. The activity of the active form in HCC was 61 +/- 21 (SD) pmol/min/mg microsomal protein, while it was only 17 +/- 9.8 pmol/min/mg protein in the liver tissue from the controls; the difference was significant (P less than 0.005). The total activity of the reductase was also higher in HCC although the difference was not significant. The microsomal contents of the enzyme protein also were not significantly different. The rate of cholesterol biosynthesis was 307 +/- 81 pmol/h/mg tissue in HCC and 79.6 +/- 52 in normal liver tissue, indicating a significant increase in the rate in HCC (P less than 0.001). Thus, enhanced synthesis of cholesterol in human HCC seems to result partly from an increase in the active form of the reductase. |
| Increase in vulnerability to oxidative damage in cholesterol-modified erythrocytes exposed to t-BuOOH Lopez-Revuelta, A., J. I. Sanchez-Gallego, et al. (2005), Biochim Biophys Acta 1734(1): 74-85. Abstract: During the course of radical oxidation, cholesterol may exert seemingly contradictory effects. In order to gain a better understanding of the relationship between cholesterol levels and membrane susceptibility to oxidative damage induced by reactive oxygen species (ROS), here we analyze the integrity and structural stability of cholesterol-modified (enriched or depleted) and unmodified (control) erythrocytes exposed to tert-butyl hydroperoxide. The oxidant significantly increased ROS production, with almost complete oxidation of hemoglobin and a reduction in GSH content in the different erythrocyte groups at 2 mM concentration. These changes were accompanied by losses of cholesterol and total phospholipids, the main decreases being in phosphatidylethanolamine and phosphatidylcholine. The highest lipid loss was found in the cholesterol-depleted group. Fatty acid analyses revealed changes only in peroxidized cholesterol-modified erythrocytes, with decreases in linoleic and arachidonic acids. Fluorescence anisotropy studies showed an increase in the fluidity of the negatively charged surface of peroxidized control erythrocytes. Increased hemolysis and a positive correlation between cellular osmotic fragility and malondialdehyde contents were found in all peroxidized groups. These findings provide evidence that the modification of cholesterol levels in the erythrocyte membrane has provoking effects on peroxidation, with corresponding increases in oxidative damage in the treated cell, possibly as a consequence of lipid bilayer destabilization. |
| Increase of an endogenous inhibitor of nitric oxide synthesis in serum of high cholesterol fed rabbits Yu, X. J., Y. J. Li, et al. (1994), Life Sci 54(12): 753-8. Abstract: In the present study, the concentration of NG,NG-dimethylarginine (DMA), an endogenous inhibitor of nitric oxide synthesis, was measured with high-performance liquid chromatography, and the effect of hypercholesterolemia on DMA level was investigated in the high fat, high cholesterol fed rabbit. After 6 weeks on a high fat, high cholesterol diet, serum total cholesterol, triglycerides, and lipid peroxides were increased, and atherosclerosis was shown by means of morphological examination. In these rabbits with atherosclerosis, serum level of DMA was significantly raised, while serum creatine level remained normal. This study suggests that chronic hypercholesteremia may stimulate DMA production through elevation of lipid peroxides. The present results implicate endogenous DMA as a contributor to the development of atherosclerosis. |
| Increase of bile acids synthesis and excretion caused by taurine administration prevents the ovariectomy-induced increase in cholesterol concentrations in the serum low-density lipoprotein fraction of Wistar rats Kishida, T., H. Ishikawa, et al. (2003), J Nutr Biochem 14(1): 7-16. Abstract: We examined the effect of dietary taurine on the concentrations of serum cholesterol and apolipoprotein in lipoprotein fractions of Six-month-old ovariectomized, which were used as a model of hypercholesterolemia in postmenopausal woman, or sham operated rats. Taurine significantly reduced the serum total and low-density lipoprotein cholesterol concentrations only in the ovariectomized rats. In contrast, taurine significantly lowered the serum apolipoprotein B concentration and serum very low-density lipoprotein-apolipoprotein E concentration only in the sham operated rats. The serum total and high density lipoprotein-apolipoprotein E concentrations were significantly lower in the rats fed taurine than in those fed the control diet regardless of whether they had undergone ovariectomy. The esterified cholesterol level in the liver was significantly lower and the level of hepatic cholesterol 7 alpha-hydroxylase activity was significantly higher in the rats fed taurine than in those fed the control diet. The total bile acids concentration in the feces and intestinal contents of rats fed taurine were significantly higher than those in rats fed the control diet regardless of whether they had undergone ovariectomy. In the sham-rats, taurine accelerated bile acid synthesis and excretion, thereby increasing cholesterol consumption. The increased cholesterol consumption might be compensated by accelerating cholesterol synthesis and/or reducing the synthesis and release of very low-density lipoprotein from the liver. But in the ovariectomized rats, although taurine also accelerated bile acid synthesis and excretion, cholesterol demand might be compensated by excess cholesterol in the blood. |
| Increase of deoxycholate in supersaturated bile of patients with cholesterol gallstone disease and its correlation with de novo syntheses of cholesterol and bile acids in liver, gallbladder emptying, and small intestinal transit Shoda, J., B. F. He, et al. (1995), Hepatology 21(5): 1291-302. Abstract: A total of 100 nonobese and normolipidemic subjects (29 control subjects, 49 patients with cholesterol stones CSs, and 22 patients with brown pigment stones) were studied to elucidate the pathogenetic contributions of deoxycholate (DC) to supersaturated bile formation with special reference to de novo syntheses of cholesterol and bile acids in the liver. A higher proportion of DC was observed in gallbladder bile from patients with CSs (CSs; 21.7 +/- 1.4%, mean +/- SEM, vs. control subjects; 10.2 +/- 0.9%). Cholesterol saturation in bile was elevated parallel to the increase of DC (r =.48; P =.0002), irrespective of the existence of stones. In a comparison between the 52 subjects with increased DC in bile (> 10% of biliary bile acids) and the 20 subjects without the increase (< 10%), the molar percentage of cholesterol in bile was significantly higher in the former (9.4 +/- 0.5%) than in the latter (6.7 +/- 0.4%) (P <.001). Consistent with the decrease in steady-state level of low-density lipoprotein (LDL) receptor-messenger RNA (mRNA), the catalytic activity and mRNA level of microsomal hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for de novo cholesterol synthesis, were significantly lower in the former (2.9 +/- 0.3 pmol/min/mg protein) than in the latter (5.1 +/- 0.6) (P <.0001). Biliary molar percentage of bile acids was significantly lower in the former (69.8 +/- 1.1%) than in the latter (75.2 +/- 1.5%) (P <.01). However, contrary to expectations, the catalytic activity and mRNA level of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme for bile acid synthesis, were significantly higher in the former (5.8 +/- 0.4 pmol/min/mg protein) than in the latter (3.7 +/- 0.6) (P <.01). The magnitude of the impaired gallbladder emptying (control subjects; 78.4 +/- 4% vs. CSs; 58 +/- 3%; P <.0005) together with the prolonged small intestinal transit (control subjects; 126 +/- 9 minutes vs. CSs; 198 +/- 9 minutes; P <.01) correlated significantly with the increased percentage of DC in bile. It is concluded that in cholesterol gallstone disease an increase of DC in bile, linked to an impaired gallbladder emptying together with a prolonged small intestinal transit, may play a significant role in downregulating de novo cholesterol synthesis but not bile acid synthesis in the liver.(ABSTRACT TRUNCATED AT 400 WORDS) |
| Increase of high-density lipoprotein cholesterol at ovulation in healthy women Lyons Wall, P. M., N. Choudhury, et al. (1994), Atherosclerosis 105(2): 171-8. Abstract: Plasma cholesterol is believed to vary more in women than in men, with the menstrual cycle, yet our review of the literature found no consistent pattern. We examined variations in plasma lipoproteins in relation to ovarian hormones in 12 healthy, menstruating women. Twenty fasting blood samples were obtained on alternate days over one menstrual cycle; ovulation was timed by hormone measurements. Plasma was analysed enzymatically for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triacylglycerol (TAG). Low-density lipoprotein cholesterol (LDL-C) was estimated by the Friedewald formula. The greatest effect was seen in HDL-C. Concentrations increased by 12% (P < 0.001) between the times of menstruation and ovulation and remained elevated until the following premenstrual phase. The height of peak oestradiol concentrations at ovulation was significantly associated with HDL-C in that phase (r = +0.75, P < 0.01), and with mean HDL-C concentrations over the whole cycle (r = +0.65, P < 0.05). TC and LDL-C also increased at ovulation, by 9% (P < 0.005) and 11% (P < 0.025) respectively, although the effect was more transient. This study demonstrates that consistent changes in plasma lipoproteins do occur during the menstrual cycle. |
| Increase of vitamin E content in LDL and reduction of atherosclerosis in cholesterol-fed rabbits by a water-soluble antioxidant-rich fraction of Salvia miltiorrhiza Wu, Y. J., C. Y. Hong, et al. (1998), Arterioscler Thromb Vasc Biol 18(3): 481-6. Abstract: Antioxidants that prevent LDL from oxidation may reduce atherosclerosis. Salvia miltiorrhiza Bunge is a Chinese herb widely used for the treatment of atherosclerosis-related disorders. Salvianolic acid B (Sal B), a water-soluble polyphenolic antioxidant isolated from the roots of this plant, was found to scavenge 1,1-diphenyl-2-picrylhydrazyl radicals and inhibit LDL oxidation more effectively than probucol. In order to evaluate the antiatherogenic potential, New Zealand White rabbits were fed for 12 weeks a normal diet, a high cholesterol diet, a high cholesterol diet containing 1% probucol, or a high cholesterol diet containing a 5% water-soluble extract of S miltiorrhiza (SM). Both SM and probucol feeding reduced plasma cholesterol. LDLs from the SM-treated group were more resistant to Cu2+-induced oxidation and contained more vitamin E (21.7+/-2.1 mmol/micromol LDL cholesterol) than did LDLs from the high cholesterol diet group (9.6+/-1.8 nmnol/micromol LDL cholesterol) (P<.005). Endothelial damage, determined at week 6, was reduced by 53% in the SM group (P<.01). SM treatment reduced the atherosclerotic area in the abdominal aorta by 56% (P<.005) and cholesterol deposition in the thoracic aorta by 50% (P<.005). The severity of atherosclerosis in the SM group was significantly reduced after adjustment by using cholesterol exposure as an index of the cholesterol-lowering effect. This study concludes that the reduction of atherosclerosis by SM relies not only on its cholesterol-lowering effect but more heavily on its antioxidant potential to prevent endothelial damage and inhibit LDL oxidative modification in hypercholesterolemic animals. |
| Increase or decrease of HDL-cholesterol concentrations during pravastatin treatment depending on the pre-treatment HDL cholesterol levels Narita, Y., Y. Kitazoe, et al. (1997), Eur J Clin Pharmacol 52(6): 461-3. Abstract: OBJECTIVE: The effect of pravastatin was evaluated using patient data accumulated in the data base of a hospital information system (HIS). METHODS: We selected 130 patients treated with pravastatin 10 mg per day, for a minimum period of 4 weeks. RESULTS: In the t test analysis, the reduction rates of total cholesterol (TC) and low-density lipoprotein (LDL) levels for pravastatin administration were 18%, and 27%, respectively. These values were similar to previous reports. The high-density lipoprotein (HDL) level, however, did not change significantly, although previous reports have shown an elevation of HDL levels. In an attempt to explain the origin of this difference, we studied the pretreatment value dependence of the cholesterol change using regression analysis. We found that pravastatin raised the HDL level in those cases where pretreatment values were lower than 58 mg.dl-1 and reduced it for higher values. We also showed that the reductions of TC, LDL and triglyceride (TG) levels correlated positively with their pretreatment values. |