| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The effect of physical activity on serum total and low-density lipoprotein cholesterol concentrations varies with apolipoprotein E phenotype in male children and young adults: The Cardiovascular Risk in Young Finns Study Taimela, S., T. Lehtimaki, et al. (1996), Metabolism 45(7): 797-803. Abstract: Apolipoprotein E (apo E) determines serum total (TC) and low-density lipoprotein (LDL-C) cholesterol concentrations and is thus associated with coronary heart disease (CHD) risk. We studied if the effect of physical activity (PA) on serum TC and LDL-C concentrations varies with apo E phenotype in a population-based sample of children and young adults with regular PA. The study cohort consisted of subjects aged 9, 12, 15, 18, 21, and 24 years in 1986 (N = 1,498) participating in a large multicenter study of cardiovascular risk factors in children and young adults. Serum lipid concentrations were determined enzymatically, and apo E phenotypes by isoelectric focusing and immunoblotting. The composition of the diet was determined by a 48-hour recall method, and a PA index was calculated on the basis of frequency, intensity, and duration of activity assessed by a questionnaire. LDL-C (P =.0082), TC (P =.014), and the high-density lipoprotein cholesterol (HDL-C)/TC ratio (P =.0004) responses to exercise varied with apo E phenotype. The effect of PA on LDL-C, TC, or HDL/TC was not found in apo E phenotype E4/4. A moderate inverse effect of PA on TC and LDL-C and a positive effect on HDL/TC was found in subjects with E4/3 and E3/3 phenotypes. Similar but stronger associations were found between these variables within the group of E3/2 males. The effect of PA on serum lipid levels was strongest within the phenotype E3/2. These associations were not explained by dietary habits. Apo E phenotype partly determines the effect of PA on serum TC and LDL-C in Finnish male children and young adults with regular PA. |
| The effect of physical exercise on reverse cholesterol transport Leaf, D. A. (2003), Metabolism 52(8): 950-7. Abstract: High-density lipoproteins (HDL) are recognized for their role in coronary artery disease (CAD) risk reduction. Plasma HDL plays a pivotal role in the reverse cholesterol transport (RCT) process. Physical exercise is well recognized as a modality that affects HDL metabolism. The purpose of this discussion is to describe the effects of physical exercise on RCT. |
| The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators Sacks, F. M., M. A. Pfeffer, et al. (1996), N Engl J Med 335(14): 1001-9. Abstract: BACKGROUND: In patients with high cholesterol levels, lowering the cholesterol level reduces the risk of coronary events, but the effect of lowering cholesterol levels in the majority of patients with coronary disease, who have average levels, is less clear. METHODS: In a double-blind trial lasting five years we administered either 40 mg of pravastatin per day or placebo to 4159 patients (3583 men and 576 women) with myocardial infarction who had plasma total cholesterol levels below 240 mg per deciliter (mean, 209) and low-density lipoprotein (LDL) cholesterol levels of 115 to 174 mg per deciliter (mean, 139). The primary end point was a fatal coronary event or a nonfatal myocardial infarction. RESULTS: The frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group, an absolute difference of 3 percentage points and a 24 percent reduction in risk (95 percent confidence interval, 9 to 36 percent; P = 0.003). Coronary bypass surgery was needed in 7.5 percent of the patients in the pravastatin group and 10 percent of those in the placebo group, a 26 percent reduction (P=0.005), and coronary angioplasty was needed in 8.3 percent of the pravastatin group and 10.5 percent of the placebo group, a 23 percent reduction (P=0.01). The frequency of stroke was reduced by 31 percent (P=0.03). There were no significant differences in overall mortality or mortality from noncardiovascular causes. Pravastatin lowered the rate of coronary events more among women than among men. The reduction in coronary events was also greater in patients with higher pretreatment levels of LDL cholesterol. CONCLUSIONS: These results demonstrate that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels. |
| The effect of pravastatin on serum cholesterol levels in hypercholesterolemic diabetic rabbits Arbeeny, C. M. and K. E. Bergquist (1991), Biochim Biophys Acta 1096(3): 238-44. Abstract: Diabetes mellitus is associated with hyperlipidemia and increased risk of atherosclerosis. A diabetic animal model has been developed to study the effect of treatment with pravastatin, a potent HMG CoA reductase inhibitor, on plasma lipoprotein levels. Hypercholesterolemia was induced in alloxan diabetic and control rabbits by feeding a diet containing 25% casein and 10% hydrogenated coconut oil for 8 weeks. Feeding the casein-coconut oil diet to the diabetic group resulted in a 5-fold increase in serum cholesterol levels, which was not statistically different from the nondiabetic group fed this diet. However, in the diabetic group, there was more cholesterol in the VLDL fraction and less in LDL as compared to the nondiabetic group. Serum triacylglycerol levels in the diabetic rabbits were variable and ranged from 58-943 mg/dl. The diabetic and nondiabetic animals were then treated with pravastatin at a dose of 10 mg/kg per day for 21 days. In the nondiabetic group, pravastatin treatment significantly lowered serum and LDL cholesterol concentrations by 28.5% (52.3 mg/dl, P less than 0.05) and 36.2% (40.7 mg/dl, P less than 0.05) respectively, relative to the placebo group. Serum and VLDL triacylglycerol levels in the nondiabetic group were also significantly decreased following pravastatin treatment. In the diabetic group, serum and LDL cholesterol levels were decreased by 37.0% (69.1 mg/dl, P less than 0.05) and 52.7% (32.1 mg/dl, P less than 0.01), respectively, relative to the diabetics given the placebo. Pravastatin treatment did not adversely affect serum glucose levels. Thus, pravastatin treatment was effective in controlling the hypercholesterolemia present in these diabetic animals. |
| The effect of probucol and clofibrate on hepatic cholesterol metabolism Shand, J. H. and D. W. West (1994), Biochem Soc Trans 22(2): 111S. |
| The effect of probucol and its new analog on cholesterol and lipoprotein metabolism in rabbit cultured hepatocytes Mambetisaeva, E. T., E. I. Kosenkov, et al. (1994), Biokhimiia 59(1): 118-25. Abstract: The effects of the well-known hypolipidemic drug probucol and its new analog K5 on cholesterol and bile acid metabolism in cultured rabbit hepatocytes have been studied. Probucol (100 microM) inhibited by 24-28% the 2-14Cacetate incorporation into cholesterol. In contrast, the probucol analog K5 used at the same concentration did not affect the cholesterol synthesis but reduced by 44-55% the VLDL-apolipoprotein B (apo-B) secretion into the culture medium. Neither of the drugs influenced the 14Cleucine incorporation into cellular proteins. In addition, probucol (100 microM) stimulated by 29-64% the specific uptake of 125I-labelled LDL into the cells and increased the glycocholic and taurocholic acid synthesis by 29-93% and 45-77%, respectively, the total bile acid synthesis from 4-14Ccholesterol synthesis being increased by 25-36%. K5 had no appreciable effect on this process. The data obtained suggest that the enhanced specific uptake of LDL into hepatocytes as well as the slight inhibition of cholesterol synthesis and stimulation of cholesterol conversion into bile acids can, at least partly, account for the hypolipodemic effect of probucol. The observed reduction in the secretion of the hepatocyte apo-B containing lipoprotein by the probucol analog K5 suggests it to be a potentially hypolipodemic compound. |
| The effect of probucol on oxidized cholesterol disposition in hyperlipidaemic patients Inouye, M., H. Hashimoto, et al. (1998), J Int Med Res 26(5): 233-8. Abstract: Probucol is a cholesterol-lowering and antioxidant drug that has been shown to inhibit or delay the progression of atherosclerosis. This antiatherosclerotic effect may result from the removal of oxidized cholesterol on the surface of low-density lipoprotein (LDL). To investigate whether probucol transfers oxidized cholesterol from LDL to urine, urine samples were obtained from five patients with hypercholesterolaemia treated with 500-mg probucol orally daily and from five healthy controls. Using gas chromatography-mass spectrometry, we identified cholesteryl-6-(2,6-di-tertiary butylphenol-4)-thioether (CT) in the urine samples from patients with hypercholesterolaemia but not from healthy controls. This result suggests that probucol is hydrolysed to form 4-mercapto-2,6-di-tertiary butylphenol (MBP) which conjugates with cholesterol-5 alpha, 6 alpha-epoxide, oxidized cholesterol, resulting in the formation of CT in vivo. In addition to its hypolipidaemic and antioxidant actions, probucol may act to prevent atherosclerosis by increasing the urinary excretion of oxidized cholesterol. |
| The effect of progesterone on metabolism of cholesterol esters in macrophages cultured with acetylated low density lipoproteins Dolgov, A. V., M. I. Dushkin, et al. (1990), Vopr Med Khim 36(4): 38-41. Abstract: Effect of progesterone on esterification of free cholesterol, on content of free cholesterol and its esters was studied in rat macrophages, cultivated in presence of acetyl-derivatives of low density lipoproteins (Ac-LDL), as well as on mobilization of cholesterol from macrophages. Progesterone at a dose of 0.5-10 micrograms per I ml of cultivating medium caused dose-dependent inhibition of I-14C-oleate incorporation into cholesterol esters of macrophages cultivated with Ac-LDL (50 micrograms of protein/ml). In the medium free of LDL progesterone caused an increase of cholesterol in macrophages by 45%, while addition of 100 micrograms/ml LDL led to a decrease of free cholesterol by 20% of the initial level. If macrophages pre-enriched with 4-C14-cholesterol were cultivated in LDL containing medium, progesterone increased the 4-14C-cholesterol liberation into medium and decreased the cholesterol content in macrophages. Under conditions of macrophages incubation in the LDL-free medium, progesterone increased the free cholesterol content in these cells but did not affect the 4-14C-cholesterol liberation into medium. The data obtained suggest that the progesterone-induced inhibition of free cholesterol esterification may increase its mobilization from macrophages only if the LDL acceptor function is unaltered. |
| The effect of protamine on cholesterol, triglycerides and blood serum proteins during the dynamics of experimental hypercholesterolemia Bozhko, G., P. V. Voloshin, et al. (1993), Vopr Med Khim 39(3): 8-12. Abstract: Content of total proteins, cholesterol, and triglycerides was studied in the blood serum and lipoprotein fractions of rabbits after administration of protamine within 1, 3 and 7 months of hypercholesterolemia development. The protamine effect was accompanied by "equalization" of cholesterol and triglyceride concentrations, as compared with their alteration in hypercholesterolemia, by stabilization of their content in various periods of the disease, but at the higher level than that of intact animals. The phenomenon observed occurred mainly in lipid components of LDL and VLDL subfractions. Analysis of alterations in the content of cholesterol and proteins in HDL and apo B-containing fractions showed that administration of protamine during long-term hypercholesterolemia led to development of antiatherogenic symptoms. Proatherogenic alterations in lipoprotein composition, developed during hypercholesterolemia, appear to be inhibited by protamine. |
| The effect of protons or calcium ions on the phase behavior of phosphatidylserine-cholesterol mixtures Wachtel, E. J., N. Borochov, et al. (1991), Biochim Biophys Acta 1066(1): 63-9. Abstract: The influence of protons or calcium ions on the miscibility of cholesterol in phosphatidylserine has been examined using differential scanning calorimetry and X-ray diffraction. At pH 2.6, where the carboxyl group of the serine moiety is protonated, two endothermic transitions are observed in cholesterol-phosphatidylserine mixtures. The midpoint of the first is at 35 degrees C in the absence of cholesterol and decreases to approx. 15 degrees C for molar fraction of cholesterol 0.5. The second transition is centered at approx. 44 degrees C, almost independent of cholesterol content. The two lower temperature phases are lamellar and the high temperature phase has hexagonal symmetry. Cholesterol is more miscible in protonated phosphatidylserine than in the sodium form: cholesterol crystals are detected at a molar ratio of phosphatidylserine to cholesterol of about 1.7:1 as compared to about 2.3:1 at neutral pH. In the presence of calcium ions (1.3 Ca2+ per phosphatidylserine), a lamellar phase is observed with layer spacing 53 A which is independent of temperature (25 degrees C-65 degrees C) and of cholesterol content. Calcium ions cause reduced cholesterol solubility: crystallites are detected already at a molar ratio of 4:1. |
| The effect of pure and long-stored commercial cholesterol on the binding of very low density and low density lipoproteins by rabbit hepatocytes (in vitro research) Volgushchev, S. A., V. A. Kosykh, et al. (1991), Biull Eksp Biol Med 111(3): 250-1. Abstract: Effects of pure and long-stored commercial cholesterol feeding on rabbit plasma cholesterol level, on rabbit hepatocyte cholesterol esters levels, and on receptor activity of rabbit hepatocytes were investigated in three experimental groups. In comparison with control, the cholesterol levels in plasma of rabbits, fed with pure and long-stored cholesterol, were 3 and 15 times higher accordingly. Free cholesterol and cholesterol esters concentrations were enhanced in hepatocytes of rabbits fed with pure cholesterol (1.4 and 2.3 times, accordingly, p 0.05) and much more enhanced in hepatocytes of rabbits fed with long-stored cholesterol (4.5 and 24 times, accordingly, p less than 0.05). Specific binding of 125-1-labeled VLDL and LDL to rabbit hepatocytes was decreased in experimental groups by 20% and 32%, accordingly in the first group and by 40% and 77%, accordingly in the second group. |
| The effect of reduced cholesterol on coronary arteries Landmark, K. and A. Reikvam (1998), Tidsskr Nor Laegeforen 118(24): 3805-9. Abstract: High levels of cholesterol increase the influx of calcium ions into vascular smooth muscle cells, thereby increasing vascular tone and resistance. Simultaneously, endothelium-dependent (NO-mediated) vasodilatation is inhibited in the arteries. Brief reductions in cholesterol induced by dietary intervention or with lipid lowering therapy normalize endothelial dysfunction, and myocardial perfusion will increase well before any beneficial effects on atherosclerosis are detected. These phenomena may explain, at least in part, that in spite of even small differences in angiographic findings between patients who have undergone treatment and those who have not, lowering lipids will cause major reductions in cardiovascular events. Lowering the levels of cholesterol will alter the content and composition of atherosclerotic plaques, thereby making them more stable. The result is probably a substantial reduction in the frequency of plaque rupture, and if rupture should occur, the thrombotic mechanisms will probably be weaker. Consequently, the risk of a thrombotic occlusion of a coronary vessel will be reduced. |
| The effect of reduced sodium intake on blood pressure, body weight, renin, aldosterone, catecholamines, cholesterol and triglycerides. A meta-analysis Graudal, N. A., A. M. Galloe, et al. (1999), Ugeskr Laeger 161(17): 2526-30. Abstract: The purpose of the present study was to estimate the effects of reduction in sodium intake on blood pressure, hormones and lipids. Data were extracted from randomised studies and statistically integrated in a meta-analysis. In 58 trials of hypertensive persons, a reduction in sodium intake of 118 mmol reduces systolic BP by 3.9 mmHg (CI: 3.0-4.8) (p < 0.0001) and diastolic BP by 1.9 mmHg (CI: 1.3-2.5) (p < 0.0001). In 56 trials of normotensive persons, the reduction in sodium intake reduced SBP by 1.2 mmHg (CI: 0.6-1.8) (p < 0.0001) and DBP by 0.26 mm Hg (CI: -0.3-0.9) (p = 0.12). Plasma renin and alsterone increased by a factor of three to four (p < 0.0001). There was a significant decrease in body weight and an increase in noradrenaline, cholesterol and LDL cholesterol. In conclusion the present results do not warrant a general recommendation of reducing sodium intake. |
| The effect of reduction of lipoprotein (a) on cellular cholesterol synthesis in non-diabetic and type 2 diabetic subjects Gilligan, S., D. Owens, et al. (1995), Biochim Biophys Acta 1254(2): 187-92. Abstract: This study investigates the effect of Lipoprotein (a) (Lp(a)) on cellular cholesterol synthesis in non-diabetic (n = 7) and Type 2 (non-insulin-dependent) diabetic subjects (n = 7) with elevated levels of Lp(a) (> 20 mg/dl). N-Acetylcysteine was used to lower Lp(a) in the control subjects and their lipoproteins were re-examined after 7 days of treatment. Low-density lipoprotein (LDL) was isolated and separated from Lp(a) by sequential ultracentrifugation. Regulation of cellular cholesterol synthesis was assessed by measuring incorporation of 14Cacetate into mononuclear leucocytes in the presence of LDL and Lp(a). Cellular cholesterol content was determined by a fluorometric assay. Delivery of cholesterol to the cell was examined using 3Hcholesteryl oleate-labelled LDL or Lp(a). LDL (5 micrograms/ml) from non-diabetic subjects suppressed cellular cholesterol synthesis by 66.2%, while Lp(a) at a similar concentration only suppressed cholesterol synthesis by 5.8% (P < 0.001). At a concentration of 20 micrograms/ml, Lp(a) suppressed cholesterol synthesis by 31.7%. The situation was similar in the diabetic subjects. Serum LDL cholesterol in non-diabetic subjects was 4.2 +/- 0.5 mmol/l and the LDL esterified/free cholesterol ratio was 2.6 +/- 0.2. Following treatment with N-acetylcysteine, LDL cholesterol did not change, while Lp(a) decreased significantly by 24% (P < 0.05). The LDL esterified/free cholesterol ratio decreased to 2.2 +/- 0.2 (P < 0.05) and there was a significant increase in the ability of the subjects LDL to inhibit cellular cholesterol synthesis (P < 0.05). There was a significant negative correlation between plasma Lp(a) and the ability of the patients' LDL to inhibit cellular cholesterol synthesis (r = -0.68, P < 0.01). 3HCholesteryl-oleate-LDL (5 micrograms/ml) delivered 266 +/- 13 ng cholesteryl oleate/mg cell protein, while it took 20 micrograms of 3Hcholesteryl oleate-labelled-Lp(a) to deliver a similar concentration (315 +/- 21 ng cholesteryl oleate/mg cell protein). In conclusion it appears possible that the atherogenicity of Lp(a) may be associated with its effect on the LDL receptor which alters LDL receptor uptake, LDL composition and cellular cholesterol synthesis. |
| The effect of sarcolemmal cholesterol content on intracellular calcium ion concentration in cultured cardiomyocytes Bastiaanse, E. M., D. E. Atsma, et al. (1994), Arch Biochem Biophys 313(1): 58-63. Abstract: In this study the relationship between sarcolemmal free cholesterol content and intracellular calcium ion concentration (Ca2+i) was explored. In cultured neonatal rat cardiomyocytes the cellular free cholesterol content was modulated by treatment with liposomes. Using cholesterol-rich or cholesterol-free liposomes, sarcolemmal free cholesterol content was raised or diminished, respectively. An increased sarcolemmal free cholesterol content resulted in a decreased sarcolemmal fluidity, whereas cholesterol depletion resulted in an increase in sarcolemmal fluidity. Cholesterol enrichment was associated with an increased Ca2+i, while cholesterol depletion resulted in a decreased Ca2+i. The membrane mobilizing agent 2-(2-methoxyethoxy)ethyl 8-(cis-2-c-octylcyclopropyl)-octanoate (A2C) caused an increase in sarcolemmal fluidity, and an increased Ca2+i. Thus, although sarcolemmal cholesterol depletion as well as A2C treatment increased sarcolemmal fluidity, their effects on Ca2+i are opposite. These results indicate that the effect of sarcolemmal free cholesterol content on Ca2+i is not mediated by sarcolemmal fluidity. The mechanisms responsible for the observed results are: (i) activated Ca2+ channels when the sarcolemma is enriched with cholesterol, (ii) most likely a stimulated Ca(2+)-ATPase activity when the sarcolemma is depleted of cholesterol, and (iii) inhibited Na+/Ca2+ exchanger activity when A2C is incorporated in the sarcolemma. |
| The effect of sarcolemmal cholesterol content on the tolerance to anoxia in cardiomyocyte cultures Bastiaanse, E. M., L. J. van der Valk-Kokshoorn, et al. (1994), J Mol Cell Cardiol 26(5): 639-48. Abstract: To determine whether the sarcolemmal-free cholesterol content influences the tolerance to anoxia in cultured neonatal rat cardiomyocytes, we modulated the free cholesterol content of the cultures, and determined the time course of anoxia-induced cell death. Incubation for 5 h with liposomes having a free cholesterol to phospholipid molar ratio of 2, 0.5 and 0, resulted in a change of cellular free cholesterol content by +54.7 +/- 5.8% (P < 0.001), by -5.2 +/- 6.3% (n.s.), and by -22.1 +/- 4.9% (P < 0.01), respectively, when compared to cultures incubated without liposomes (control). In cells which were loaded with cholesterol, it was verified that the extra cholesterol was transferred predominantly to the sarcolemma, which was associated with a decrease in sarcolemmal fluidity. In cells which underwent cholesterol reduction it was verified that free cholesterol was retracted selectively from the sarcolemma, associated with an increase in sarcolemmal fluidity. Cellular enrichment with free cholesterol caused a delay of anoxia-induced release of lactate dehydrogenase (LDH): the time at which half-maximal release of LDH was reached (LDH50%) occurred later by 35.5 +/- 3.4 min (P < 0.001) compared to anoxic control cultures. Cholesterol reduction diminished the tolerance to anoxia: LDH50% occurred earlier by 36.4 +/- 7.8 min (P < 0.01), compared to anoxic control cultures. Cultures which were incubated with liposomes having a free cholesterol to phospholipid molar ratio of 0.5 had unchanged sarcolemmal free cholesterol content, unchanged sarcolemmal fluidity, and an unchanged LDH50% during anoxia in comparison to control cultures, excluding any effect of the incubation with liposomes per se. The present study indicates that the sarcolemmal free cholesterol content of cardiomyocytes is a determinant of their tolerance to anoxia. |
| The effect of side-chain analogues of cholesterol on the thermotropic phase behavior of 1-stearoyl-2-oleoylphosphatidylcholine bilayers: a differential scanning calorimetric study Vilcheze, C., T. P. McMullen, et al. (1996), Biochim Biophys Acta 1279(2): 235-42. Abstract: In this study we have examined the effects of analogues of cholesterol differing with respect to alkyl side-chain length and structure on the thermotropic phase behavior of bilayers formed from 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), an important subclass of naturally occurring phosphatidylcholines (PCs). The synthetic sterols we studied contained either a terminally unbranched (n-series) or a single methyl-branched (iso-series) side chain of 3 to 10 carbon atoms. The phase transition behavior was examined by high-sensitivity differential scanning calorimetry (DSC). The main phase transition endotherm of SOPC/sterol bilayers consists of superimposed sharp and broad components, which represent the hydrocarbon chain melting of sterol-poor and sterol-rich phospholipid domains, respectively. The transition temperature and the cooperativity of the sharp component are moderately reduced upon sterol incorporation and the enthalpy decreases to zero when sterol levels of 20-30 mol% are reached. The enthalpy of the broad component transition initially increases to a maximum around 25 or 25-30 mol% sterol and thereafter decreases with further increases in sterol concentration. However, the broad transition of SOPC bilayers containing both short (C-22, i-C5 and n-C3) and long (i-C9 and i-C10) side-chain sterols still persists at levels of 50 mol% sterol. Thus the effective stoichiometry of SOPC-sterol interactions varies with changes in sterol alkyl side-chain length. The incorporation of short linear or branched side-chain sterols (C-22, n-C3, n-C4, i-C5) causes the broad component transition temperature and cooperativity to decrease dramatically, whereas the incorporation of medium- and long-chain sterols in both the n- and iso-series has less effect on the transition temperature and cooperativity of the broad component. Overall, no significant differences were found between the n- and iso-series sterols for a given side-chain length. A comparison of the phase behavior of dipalmitoylphosphatidylcholine (DPPC)/sterol (McMullen et al. (1995) Biophys. J. 69, 169-176) and SOPC/sterol mixtures indicates that the primary factor responsible for changes in the thermotropic phase behavior of these systems is the extent of the hydrophobic mismatch between the sterol and the host lipid bilayer. However, sterol miscibility in PC bilayers, and thus the stoichiometry of lipid-sterol interactions, also appears to depend on the degree of unsaturation of the host lipid bilayer. |
| The effect of simvastatin on HDL cholesterol in hyperlipidemic patients. Evidence of a relationship with the changes in serum triglyceride level Branchi, A., A. Rovellini, et al. (1996), Int J Clin Pharmacol Ther 34(9): 384-9. Abstract: The main effect of simvastatin is the decrease of serum cholesterol due to the reduction of LDL. A decrease of serum triglycerides and an increase of HDL-C are commonly observed during the treatment. The reduction of triglycerides is accounted for by the increased catabolism of apo B-containing lipoproteins whereas the mechanisms bringing about the increase of HDL-C are still unknown. We treated 318 patients with primary hyperlipidemia (227 with phenotype IIa and 91 with phenotype IIb) with simvastatin 10 mg a day and after 6 weeks we found a mean 3% increase in HDL-C. HDL-C increased only in about half of the patients and the patients in whom HDL-C increased had baseline higher serum triglycerides and had a greater hypotriglyceridemic response than patients in whom HDL-C did not increase. Accordingly, HDL-C increased in type IIb patients who experienced a greater change in triglycerides than type IIa patients, in whom HDL-C did not increase significantly. Apo A-I levels did not change and apo A-I/HDL-C ratio significantly decreased. At a daily dose of 40 mg, administered to 51 treatment-resistant patients, simvastatin produced a marginally greater decrease in serum cholesterol and LDL-C, but not in serum triglycerides and HDL-C, than at the daily dose of 10 mg. An increase in HDL-C was associated with a reduction in serum triglycerides. The decrease in apo A-I/HDL-C ratio suggests that the increase in HDL-C after simvastatin must be regarded as an enrichment of the cholesterol core of HDL particles. The effect is likely to be due to the decrease of the serum concentration of VLDL bringing about a reduction of cholesterol transfer from apo A-I to apo B-containing lipoproteins. |
| The effect of simvastatin treatment on the amyloid precursor protein and brain cholesterol metabolism in patients with Alzheimer's disease Hoglund, K., K. M. Thelen, et al. (2005), Dement Geriatr Cogn Disord 19(5-6): 256-65. Abstract: During the last years, several clinical studies have been published trying to elucidate the effect of statin treatment on amyloid precursor protein (APP) processing and metabolism of brain cholesterol in Alzheimer's disease (AD) in humans. We present an open biochemical study where 19 patients with AD have been treated with simvastatin (20 mg/day) for 12 months. The aim was to further investigate the effect of simvastatin treatment on cerebrospinal fluid (CSF) biomarkers of APP processing, AD biomarkers as total tau and tau phosphorylated at threonine 181, brain cholesterol metabolism as well as on cognitive decline in patients with AD. Despite biochemical data suggesting that treatment with 20 mg/day of simvastatin for 12 months does affect the brain cholesterol metabolism, we did not find any change in CSF or plasma levels of beta-amyloid (Abeta)(1-42). However, by analysis of APP isoforms, we found that statin treatment may favor the nonamyloidogenic pathway of APP processing. The relevance and mechanism between statin treatment and AD has to be further elucidated by using statins of different lipophility in different dosages over a longer period of time. |
| The effect of smoking on post-heparin lipoprotein and hepatic lipase, cholesteryl ester transfer protein and lecithin:cholesterol acyl transferase activities in human plasma Freeman, D. J., M. J. Caslake, et al. (1998), Eur J Clin Invest 28(7): 584-91. Abstract: INTRODUCTION: Smoking is associated with dyslipidaemia, particularly raised plasma triglycerides and reduced high-density lipoprotein (HDL)-cholesterol and a delayed clearance of triglyceride in fat tolerance tests. The aim of this study was to investigate whether these phenomena could be explained by a reduced lipoprotein lipase activity in smokers. METHODS: A group of 40 healthy individuals plasma cholesterol 5.07 (SD 0.90) mmol L-1, plasma triglyceride 1.02 (SD 0.39) mmol L-1) was studied to examine the effects of smoking on plasma enzyme activities, particularly post-heparin lipase activities. The group comprised 20 smokers and 20 non-smokers, who were matched for age, gender and body mass index (BMI). RESULTS: Post-heparin lipoprotein lipase (LPL) activity 3.89 (SD 1.58) vs. 5.85 (SD 2.30) mumol free fatty acids (FFA) mL-1 h-1, P < 0.005, but not post-heparin hepatic lipase (HL) activity, was reduced in smokers. Plasma cholesteryl ester transfer protein (CETP) activity and lecithin: cholesterol acyl transferase (LCAT) activity were measured in a subgroup of 18 individuals, comprising nine smokers with nine matched non-smokers. There was no difference in CETP activities between two groups, but smokers had a significantly reduced plasma LCAT activity 112 (SD 23) vs. 152 (SD 24) nmol cholesterol mL-1 h-1, P < 0.005. In both smokers (r=-0.53, P < 0.05) and non-smokers (r=-0.54, P < 0.05), HDL2 concentration was negatively associated with HL activity. In non-smokers, HDL3 concentration was negatively associated with CETP activity (r= -0.77, P < 0.05), whereas in smokers HDL3 concentration was negatively associated with LCAT activity (r= -0.78, P < 0.050). CONCLUSION: It was shown by direct measurement that the activity of plasma post-heparin LPL is reduced in smokers, independently of age, gender and BMI. It is concluded that this enzyme perturbation associated with smoking may contribute to the development of the atherogenic lipoprotein phenotype seen in smokers. |