| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
| First Page | Previous Page | Next Page | Last Page |
| Effect of lowered cholesterol on the course of coronary heart disease. An analysis of the results of controlled, angiographically documented intervention studies Stierle, U., K. Schwabe, et al. (1995), Dtsch Med Wochenschr 120(48): 1652-9. Abstract: AIM: To find out from published reports whether the tendency of coronary heart disease (CHD) to progress can be retarded by lowering total and LDL cholesterol concentrations. METHODS: After a data-base search a meta-analysis was undertaken of all those randomized, controlled and angiographically documented studies which contained informations about the effect of cholesterol reduction on the course of CHD over a period of at least 2 years. A total of 12 studies covering 3781 patients met the stated criteria. RESULTS: The different lipid-lowering measures (usually drugs) achieved a statistically significant reduction of the number of patients with progression of the coronary angiographic findings and a significant increase in the number of those with actual regression. The number of coronary incidents, such as myocardial infarction, unstable angina, sudden cardiac death, necessary aortocoronary bypass operations or percutaneous transluminal coronary angioplasty was lower by 34% in the groups with measures to influence cholesterol metabolism than in the untreated groups. In the studies in which coronary arteriograms were evaluated quantitatively there was an annual increase in the mean degree of stenosis of 1.01% in the untreated and 0.37% in the treated groups. CONCLUSIONS: The difference in the increase of the mean degree of stenosis is probably not only important because of the resulting haemodynamic changes in myocardial perfusion. The quantitatively only slightly increased trend towards progression in the untreated groups can be interpreted as a marker for an active process of atherogenesis with a tendency of plaques to break off and of plaque thromboses. |
| Effect of lowering serum cholesterol on the composition of surfactant in adult rat lung Davidson, K. G., S. M. Acton, et al. (1997), Am J Physiol 272(1 Pt 1): L106-14. Abstract: Treatment of rats with 10 mg.kg body wt-1 day-1 4-aminopyrazolo3,4-dpyrimidine (APP) for 2 days markedly reduced serum cholesterol and phospholipids. This was associated with large decreases in the principal component of alveolar surfactant, the disaturated phospholipids (DSP), in the lamellar body and in the tubular myelin-rich and -poor alveolar fractions, but with no concomitant change in cholesterol or surfactant protein A. These decreases in DSP were associated with a decrease in the synthesis of surfactant phospholipids. Despite these large changes in composition of alveolar surfactant, we could detect no change in either static or dynamic lung compliance. However, the treatment markedly increased both the minimum and maximum surface tension of the lipid extract of the tubular myelin-rich fraction, as measured by bubble surfactometry. Whereas these changes appeared unimportant in the isolated perfused lung at resting tidal volume, they were associated with edema after an increase in tidal volume. The ability of APP to inhibit phospholipid synthesis selectively makes it a useful tool in investigating the surfactant system. |
| Effect of low-saturated fat, low-cholesterol dietary intervention on fatty acid compositions in serum lipid fractions in 5-year-old children. The STRIP project Salo, P., J. Viikari, et al. (1999), Eur J Clin Nutr 53(12): 927-32. Abstract: OBJECTIVE: To evaluate the effect of dietary low-saturated fat, low-cholesterol intervention on fat intake and fatty acid compositions in serum cholesterol ester (CE), phospholipid (PL) and triglyceride (TG) fractions in five-year-old children. DESIGN AND SUBJECTS: The STRIP project is a prospective, randomised intervention project in which 1062 seven-month-old infants were recruited from the well-baby clinics. 764 children participated in the 5-year follow-up; 202 of them were randomly selected for this study. Diet was assessed with 4-d dietary records. Serum CE, PL and TG fatty acid compositions were analysed with gas-liquid chromatography. RESULTS: Saturated fat intake of intervention children (mean (confidence interval)) (girls 11.9 (11.2-12.6) % of energy intake (E%); boys 12.5 (11.9-13.1)) was lower than that of the control children (girls 14.4 (13.7-15.2) E%; boys 15.0 (14.3-15. 8) E%) (P=0.0001 for the difference between intervention and control groups). The intake of unsaturated fat differed only slightly. Dietary ratios of polyunsaturated to saturated fatty acids (PS ratios) of the intervention and control diets were 0.44 and 0.33, respectively (P=0.0001). Furthermore, serum cholesterol concentrations of the intervention and control children differed (4. 28 (4.13-4.43) mmol/L vs 4.49 (4.35-4.63) mmol/L; P=0.04). Relative proportion of saturated fatty acids in serum TG was lower (34.9% vs 36.3%; P=0.04) and that of n-6 polyunsaturated fatty acids higher (13.9% vs 12.4%; P=0.0004) in the intervention than in the control children, whereas serum CE and PL fatty acid compositions of intervention and control groups were closely similar. However, intake of linoleic acid correlated better with serum linoleic acid relative content in the CE fraction (r=0.36; P=0.0001) than in the PL (r=0.27; P=0.0002) or in the TG (r=0.23; P=0.0016) fraction. CONCLUSIONS: Intervention resulted in decreased intake of saturated fatty acids and lowered serum total and LDL cholesterol concentrations. Of serum lipid fractions, TG fatty acid composition was the most sensitive and parallelled the findings in dietary food records. |
| Effect of LpA-I composition and structure on cholesterol transfer between lipoproteins Meng, Q. H., D. L. Sparks, et al. (1995), J Biol Chem 270(9): 4280-7. Abstract: The effect of high density lipoprotein composition on the rates of unesterified cholesterol exchange between low density lipoproteins (LDL) and well-defined homogeneous discoidal lipoproteins (LpA-I) reconstituted with phosphatidylcholine, cholesterol, and apolipoprotein A-I (apoA-I) has been investigated. LpA-I containing cholesterol and 2, 3, and 4 apoA-I molecules per particle differed in their ability to accept or donate cholesterol. A significant cholesterol exchange occurs between LDL and Lp2A-I (7.8 and 9.6 nm), while there is little or no cholesterol exchange detectable between LDL and Lp3A-I (10.8 and 13.4 nm) and Lp4A-I (17.0 nm) complexes. The cholesterol transfer from LDL to the cholesterol-free Lp2A-I (9.6 nm), Lp3A-I (13.4 nm), and Lp4A-I (17.0 nm) particles also shows significant cholesterol transfer to Lp2A-I, while there is no detectable transfer to Lp3- and 4A-I particles. The rates of cholesterol transfer to cholesterol-free and cholesterol-containing Lp2A-I appear to differ significantly. Cholesterol transfer from LDL to cholesterol-free Lp2A-I is zero order with respect to acceptor concentrations when the Lp2A-I/LDL ratio is above 10. Transfer rates from LDL to cholesterol-free Lp2A-I are faster for the smaller Lp2A-I (8.5 nm) than to the larger Lp2A-I (9.7 nm) and exhibit half-times (t1/2) at 25 degrees C of 4.0 and 5.3 h, respectively. In contrast, cholesterol transfer from LDL to cholesterol-containing Lp2A-I remains dependent upon acceptor concentrations to an acceptor/donor particle ratio of 80. In addition, transfer from LDL to cholesterol-containing Lp2A-I is faster to the 9.6 nm than to 7.8 nm particles, with t1/2 of 1.4 and 2.3 h, respectively. The rates of cholesterol transfer from Lp2A-I to LDL are higher than in the opposite direction, in particular for the small Lp2A-I (7.8 nm), which has a t1/2 of approximately 50 min. The results show that changes in the composition and structure of apoA-I-containing particles have a significant effect on inter-lipoprotein exchange of cholesterol. This suggests that the kinetics of cholesterol transfer to and from reconstituted discoidal LpA-I particles cannot be fully explained by passive aqueous diffusion. |
| Effect of macrophage-derived mouse ApoE, human ApoE3-Leiden, and human ApoE2 (Arg158-->Cys) on cholesterol levels and atherosclerosis in ApoE-deficient mice Van Eck, M., N. Herijgers, et al. (2000), Arterioscler Thromb Vasc Biol 20(1): 119-27. Abstract: The effect of monocyte/macrophage-derived wild-type mouse apolipoprotein E (apoE), human apoE3-Leiden, and human apoE2 on serum cholesterol levels and the development of atherosclerosis in apoE-deficient (apoe-/-) mice was investigated by using bone marrow transplantation (BMT). At 4 weeks after BMT, murine apoe+/+ bone marrow reduced serum cholesterol levels by 87% in apoe-/- mice, whereas macrophage-derived human apoE3-Leiden and human apoE2 induced a maximal, transient reduction of 35% and 48%, respectively. At 4 months after BMT, atherosclerosis was 23-fold (P<0.001) reduced in apoe+/+-->apoe-/- mice, whereas no significant reduction in apoE3-Leiden.apoe-/--->apoe-/- and apoE2.apoe-/--->apoe-/- mice could be demonstrated. A highly significant decrease in serum cholesterol levels (78% reduction) and atherosclerosis (21-fold, P<0. 001) was found in apoE3-Leiden.apoe-/- animals expressing high levels of apoE in multiple tissues, whereas apoE2 was ineffective even at high concentrations. Furthermore, in contrast to apoE-deficient macrophages, cholesterol efflux from apoE2 or apoE3-Leiden macrophages was not impaired. In conclusion, apoE3-Leiden as well as apoE2 are less effective in reducing cholesterol levels and atherosclerosis in apoe-/- animals, compared with apoe+/+, with apoE2 |
| Effect of matrix lipid chain length on liposomes containing cholesterol and ganglioside GM1: implications in drug delivery Bedu-Addo, F. K. and L. Huang (1996), J Pharm Sci 85(7): 714-9. Abstract: Incorporation of ganglioside GM1 into liposomes composed of phosphatidylcholine (PC) and cholesterol significantly increases their blood circulation time. Dipalmitoyl PC (DPPC) and distearoyl PC (DSPC) are the most commonly used saturated phospholipids employed in the preparation of long-circulating liposome formulations. Physical studies were performed on different formulations of these liposomes in an attempt to understand the effects of the matrix lipid chain length and GM1 concentration on the use of these liposomes as long-circulating drug delivery systems. The GM1/PC mixtures existed in different physical states: a lamellar state with components exhibiting miscibility (which is the desired state for drug delivery), a mixed micellar phase, and also a smectic mesophase. GM1 is miscible with DSPC bilayers up to a concentration of 25 mol%, beyond which conversion into the metastable mesophase occurs. By 30 mol%, solubilization into the mixed micellar state occurs. With DPPC, the metastable mesophase occurs at 33-38 mol% of GM1, with mixed micelles being formed at higher concentrations. The addition of cholesterol led to an inhibition of micelle formation. This study also indicates that GM1 stabilizes DPPC bilayers while destabilizing DSPC bilayers. On the basis of the interactions of GM1 with DPPC and DSPC, a new hypothesis for stabilization of PC bilayers is proposed, which also explains the destabilization of PC with C18.0 and higher. The longest circulating GM1 liposome formulations are predicted from this study. |
| Effect of meal timing on diurnal rhythm of human cholesterol synthesis Cella, L. K., E. Van Cauter, et al. (1995), Am J Physiol 269(5 Pt 1): E878-83. Abstract: To test whether the diurnal rhythm of cholesterol synthesis in humans is entrained to meal timing, the effect of a 6.5-h delay of mealtimes was investigated in four normal lipidemic male subjects. Cholesterol fractional synthetic rate was measured by deuterium incorporation from body water using blood sampling every 2 h. The baseline was a 24-h control period in which three Western-style meals were consumed at 0700, 1150, and 1640, followed by 3 days in which meals were delayed by 6.5 h, i.e., meals consumed at 1330, 1820, and 2310 without changing the sleep-wake and light-dark cycles. Cholesterol synthesis was maximal at 2200 +/- 0200 and minimal at 1130 +/- 0050 on the baseline day. On day 1 of the shifted meals, the maximum was delayed 6.0 +/- 0.5 h and the nadir was not changed. On day 3, the maximum was delayed 8.6 +/- 3.7 h and the minimum was delayed 6.5 +/- 2.4 h from baseline. The mean amplitude of the cholesterol rhythm was significantly greater on day 3,233 +/- 35%, compared with baseline which was 109 +/- 15%. A strong negative correlation (r = -0.66 +/- 0.10) was found between the rhythms of cholesterol synthesis and cortisol during the baseline day, but there was a phase delay in the rhythm of cholesterol synthesis relative to cortisol on day 1 and day 3. Findings indicate that the 24-h variation in cholesterol synthesis is strongly dependent on meal timing. |
| Effect of melatonin on serum cholesterol and phospholipid levels, and on prolactin, thyroid-stimulating hormone and thyroid hormone levels, in hyperprolactinemic rats Esquifino, A., C. Agrasal, et al. (1997), Life Sci 61(11): 1051-8. Abstract: The effects of melatonin treatment and pituitary transplants on serum total and free cholesterol levels, cholesterol esterification index, phospholipid levels and prolactin, thyroid-stimulating hormone (TSH), thyroxine (T4) and triiodothyronine (T3) levels were examined in rats. Male rats were grafted an anterior pituitary under the kidney capsule or were sham-operated on day 30th of life. Thirty days later, the rats received 4 daily s.c. injections of melatonin (25, 50 or 100 microg/rat) or vehicle, 2 h before lights off, and were killed 15 h after the last injection, and after a 24-hour fasting period. In pituitary-grafted rats, a decrease in serum free cholesterol with unmodified total cholesterol levels, and thus an augmented cholesterol esterification index, occurred. Pituitary-grafted rats showed also an increase in serum phospholipids. In control, but not in pituitary-grafted rats, melatonin injection decreased free cholesterol without modifying total cholesterol levels. Melatonin treatment (50 microg/day or greater) normalized the augmented serum phospholipid levels found in pituitary-grafted rats and increased serum phospholipids in control rats. Melatonin injection also reduced the high serum prolactin and T3 levels found in pituitary-grafted rats, and decreased T4 concentration in control rats. Neither melatonin nor pituitary grafts modified serum TSH concentration. The results demonstrate that melatonin counteracts in part lipid disturbances of hyperprolactinemic rats and lowers free plasma cholesterol and augmented serum phospholipids in control rats. |
| Effect of melatonin on the maintenance of cholesterol homeostasis in the rat Chan, T. Y. and P. L. Tang (1995), Endocr Res 21(3): 681-96. Abstract: The effect of melatonin on cholesterol metabolism in the rat was investigated in the dietary and hypothyroid models of hypercholesterolemia. In normal and dietary hypercholesterolemia (induced by 1% cholesterol, 0.5% bile acid), melatonin treatment (12.5mg/kg i.p.) reduced total serum cholesterol concentration and total low density lipoprotein (VLDL+LDL) cholesterol. The protective action of melatonin was manifested only following the induction of cholesterolemia in such animals. Enhanced catabolism of cholesterol to bile acids is likely involved as shown by an increase in fecal bile acid excretion following melatonin treatment. Incorporation of 1-14C acetate into sterols was unaffected by melatonin treatment which suggests its lack of influence on sterol biosynthesis. In secondary hypercholesterolemia (hypothyroidism induced by 2-thiouracil), melatonin exerted a beneficial effect by increasing the HDL/total LDL cholesterol ratio. These findings suggest that the hypocholesterolemic effect of melatonin may work through the augmentation of endogenous cholesterol clearance mechanisms. This is accompanied by the lowering of the cholesterol fraction associated with low density lipoproteins. |
| Effect of membrane characteristics on phase separation and domain formation in cholesterol-lipid mixtures Pata, V. and N. Dan (2005), Biophys J 88(2): 916-24. Abstract: We examine, using an analytical mean-field model, the distribution of cholesterol in a lipid bilayer. The model accounts for the perturbation of lipid packing induced by the embedded cholesterol, in a manner similar to that of transmembrane proteins. We find that the membrane-induced interactions between embedded cholesterol molecules vary as a function of the cholesterol content. Thus, the effective lipid-cholesterol interaction is concentration-dependent. Moreover, it transitions from repulsive to attractive to repulsive as the cholesterol content increases. As the concentration of cholesterol in the bilayer exceeds a critical value, phase separation occurs. The coexistence between cholesterol-rich and cholesterol-poor domains is universal for any bilayer parameters, although the composition of the cholesterol-rich phase varies as a function of the lipid properties. Although we do not assume specific cholesterol-lipid interactions or the formation of a lipid-cholesterol cluster, we find that the composition of the cholesterol-rich domains is constant, independent of the cholesterol content in the bilayer. |
| Effect of membrane cholesterol on calcium phosphate formation in aqueous suspensions of anionic liposomes Skrtic, D. and E. D. Eanes (1992), Calcif Tissue Int 50(1): 55-60. Abstract: The present study examined the effect of membrane cholesterol on liposome-mediated calcium phosphate precipitation in metastable aqueous solutions (2.25 mM Ca2+ and 1.5 mM inorganic phosphate) at 22 degrees C, pH 7.4 and 240 mOsm. The liposomes were prepared from 7:2:X molar mixtures of phosphatidylcholine, dicetylphosphate, and cholesterol (x = 0, 1, 5, or 9) and contained either 0 or 50 mM encapsulated phosphate. The membranes were made permeable to Ca2+ by addition of the cationophore, X-537A. Changes in external Ca2+ concentration were used as the principal monitor of the course of precipitation. Without encapsulated phosphate, 7:2:X liposomes (with or without ionophore) induced no precipitation. With 50 mM encapsulated phosphate and in the presence of ionophore, precipitation significantly depended on the cholesterol level in the membrane. At 0 and 10 mole% cholesterol, precipitate developed rapidly both within and outside the liposomes. At 35 and 50 mole% cholesterol, no observable intraliposomal precipitation occurred, and extraliposomal precipitation started only after an induction period of 24 hours. Delayed extraliposomal precipitation also took place in PO4-containing liposomes without added ionophore. In this latter case, however, cholesterol was essential for this precipitation to occur with the optimum level being around 10 mole%. Suppression of ionophore-mediated intraliposomal precipitation at higher cholesterol levels could be related to the inflexible cholesterol molecules making the membrane more rigid, thereby restricting Ca-ionophore transport. This restriction could be reversed with ethanol. Delayed extraliposomal precipitation in the absence of added ionophore (or at higher cholesterol levels in its presence) could be explained by seeding from low, unobserved levels of intraliposomal precipitate formed during slow, unfacilitated Ca2+ leakage into the liposomal interior. |
| Effect of membrane environment on inhibition of acyl-CoA:cholesterol acyltransferase by a range of synthetic inhibitors Harte, R. A., S. J. Yeaman, et al. (1995), Biochim Biophys Acta 1258(3): 241-50. Abstract: The effect of the membrane environment of acyl-CoA:cholesterol acyl transferase (ACAT), an important intracellular enzyme of cholesterol metabolism, on the properties of a range of inhibitors of varying potencies was studied. ACAT activity from rat liver was solubilised with 3% deoxycholate (97% solubilised activity). After dilution into cholesterol/phosphatidylcholine liposomes (molar ratio 0.35), the assay of this reconstituted system showed linearity with protein and time. Saturation with oleoyl-CoA was achieved at 10 microM. Comparison of the potency of the ACAT inhibitors in the reconstituted assay and in a microsomal assay revealed a relationship between the lipid content of the assay and the inhibitory activity for potent inhibitors of ACAT (CI976, CL277,082, YMI7E and DuP128). This relationship was unrelated to lipophilicity of the drugs. Octimibate, lovastatin and progesterone, none of which is a potent ACAT inhibitor but which have all been described as ACAT inhibitors in the literature, all had low potencies in both assay systems. These results suggest that the lipid concentration must be taken into account when comparing potencies of ACAT inhibitors. The present data also indicate that some compounds which inhibit cholesterol esterification may do so by an indirect mechanism. |
| Effect of menopause on serum HDL-cholesterol level Sultan, N., M. Nawaz, et al. (2003), J Ayub Med Coll Abbottabad 15(3): 24-6. Abstract: BACKGROUND: There is a marked difference in the risk of coronary heart disease between men and women of reproductive age but this gap closes with advancing age. It seems likely that some factors of reproductive physiology are responsible for this. The present study was designed to evaluate the difference in HDL Cholesterol level in premenopausal and postmenopausal women in relation with change of estradiol level. METHODS: Fifty premenopausal and 50 postmenopausal women were included in the study. Estradiol was estimated by radioimmuoassay while HDL-C was estimated by Kit method. RESULTS: There was a significant (p < 0.01) decrease in the HDL-C level of the postmenopausal women (46.72 +/- 1.009) as compared with premenopausal women (63.68 +/- 1.78). CONCLUSION: HDL-C is an independent risk factor for coronary heart disease. This study favours the view that decrease in estradiol level and associated decrease in HDL-C seen in postmenopausal women may be responsible for the increased risk of coronary heart disease after menopause. |
| Effect of metoprolol and pindolol monotherapy on plasma lipid- and lipoprotein-cholesterol levels (including the HDL subclasses) in mild hypertensive males and females Szollar, L. G., I. Meszaros, et al. (1990), J Cardiovasc Pharmacol 15(6): 911-7. Abstract: Forty-five patients with mild hypertension were treated for 2 months with either metoprolol or pindolol in a randomized, blind, crossover study. The effects of metoprolol (100-300 mg/day) and pindolol (5-15 mg/day) on triglyceride (TG), cholesterol (C), high-density lipoprotein cholesterol (HDL-C), and HDL subfraction (HDL2-C and HDL3-C) levels were compared in males and females separately. Pindolol and metoprolol significantly elevated (10% above baseline level) the plasma TG level in both males and females. After metoprolol treatment, the HDL-C level remained unchanged in both sexes; however, a shift was found between HDL2-C and HDL3-C:HDL2-C decreased and a concomitant elevation in HDL3-C was observed. Pindolol significantly decreased total C, HDL-C, and HDL2-C levels in males. A similar trend (although the changes were not significant) was found in females. The results demonstrate the role of beta blockers in the inhibition of TG-rich lipoprotein elimination. These findings suggest that during long-term administration of metoprolol and pindolol, risks and benefits from beta-blocker therapy must be carefully considered. Continuous monitoring of lipid profiles is suggested during this treatment in order to avoid the potential worsening effect of beta blockers on risk factors of ischemic heart disease. |
| Effect of mevinolin and glycyrrhizinic acid on cholesterol and bile acid metabolism in cultured rabbit hepatocytes Novikov, D. K., N. A. Mukhamedova, et al. (1992), Biokhimiia 57(6): 897-903. Abstract: A comparison of effects of two hypocholesterolemic drugs--mevinolin and glycyrrhizinic acid, on cholesterol and bile acid metabolism in cultured rabbit hepatocytes has been carried out. The following parameters have been determined: i) cholesterol synthesis from 2-14Cacetate; ii) bile acid production from newly synthesized and 4-14C-labeled HDL2 cholesterol, and, iii) total cholesterol efflux into the incubation medium Mevinolin (0.5 microgram/ml) inhibited 2-14C acetate incorporation into cholesterol by more than 90%. Conversely, glycyrrhizinic acid did not influence cholesterol synthesis even when used at high (100 micrograms/ml) concentrations but stimulated the conversion of endogenous (by 37%) and exogenous (by 18%) cholesterol into bile acids and increased, in addition, the proportion of bile acids in the total sterol pool released from hepatocytes into the incubation medium. At the same time, mevinolin used at 0.5 microgram/ml decreased the bile acid production by endogenous (by 27%) and exogenous (by 40%) cholesterol. The data obtained suggest that glycyrrhizinic acid exerts hypocholesterolemic action by stimulation of cholesterol conversion into bile acids without any effect on cholesterol synthesis. As for mevinolin, it has a cholesterol-suppressing effect via a mechanism of cholesterol synthesis inhibition only. |
| Effect of micellar beta-sitosterol on cholesterol metabolism in CaCo-2 cells Field, F. J., E. Born, et al. (1997), J Lipid Res 38(2): 348-60. Abstract: CaCo-2 cells were used to address the effect of the plant sterol, beta-sitosterol, on cholesterol trafficking, cholesterol metabolism, and apoB secretion. Compared to cells incubated with micelles (5 mM taurocholate and 250 microM oleic acid) containing cholesterol, which caused an increase in the influx of plasma membrane cholesterol to the endoplasmic reticulum and increased the secretion of cholesteryl esters derived from the plasma membrane, beta-sitosterol did not alter cholesterol trafficking or cholesteryl ester secretion. Including beta-sitosterol in the micelle together with cholesterol attenuated the influx of plasma membrane cholesterol and prevented the secretion of cholesteryl esters derived from the plasma membrane. Stigmasterol and campesterol had effects similar to beta-sitosterol, although campesterol did not promote a modest influx of plasma membrane cholesterol. Including beta-sitosterol in the micelle with cholesterol decreased the uptake of cholesterol. Compared to cholesterol, 60% less beta-sitosterol was taken up by CaCo-2 cells. No observable esterification of beta-sitosterol was appreciated and the transport of the plant sterol to the basolateral medium was negligible. Cholesterol synthesis and HMG-CoA reductase activities were decreased in cells incubated with beta-sitosterol. This was associated with a decrease in reductase mass and mRNA levels. Cholesteryl ester synthesis and ACAT activities were unaltered by beta-sitosterol. Both stigmasterol and campesterol decreased reductase activity, but only campesterol increased ACAT activity. beta-sitosterol did not affect the secretion of apoB mass. The results suggest that beta-sitosterol does not promote cholesterol trafficking from the plasma membrane to the endoplasmic reticulum. beta-sitosterol interferes with the uptake of micellar cholesterol causing less plasma membrane cholesterol to influx and less cholesteryl ester to be secreted. Despite its lack of effect on cholesterol trafficking, beta-sitosterol decreases cholesterol synthesis at the level of HMG-CoA reductase gene expression. |
| Effect of micronized fenofibrate (lipantyl-200M) on synthesis of cholesterol in peripheral blood lymphocytes of patients with ischemic heart disease and hyperlipidemia Ivanova, T. N., E. D. Poliakova, et al. (1998), Biull Eksp Biol Med 125(5): 569-73. |
| Effect of micronized fenofibrate on plasma lipoprotein levels and hemostatic parameters of hypertriglyceridemic patients with low levels of high-density lipoprotein cholesterol in the fed and fasted state Genest, J., Jr., N. H. Nguyen, et al. (2000), J Cardiovasc Pharmacol 35(1): 164-72. Abstract: A randomized, double-blind, placebo-controlled study was undertaken in 20 hypertriglyceridemic men plasma triglyceride (TG), >2.3 mM with low levels (<0.9 mM) of high-density lipoprotein cholesterol (HDL-C) to investigate the ability of micronized fenofibrate (Tricor or Lipidil; 200 mg/day) to affect atherogenic and thrombogenic plasma risk factors in the fed and fasted state. Each patient underwent (a) 4 weeks of dietary stabilization, (b) 8 weeks of treatment with fenofibrate or placebo, (c) a 5-week washout period, and (d) 8-weeks of treatment with the alternative medication. An oral fat-loading test (1 g fat/kg body weight) was carried out after both treatment periods. Before treatment, patients had a mean (+/- SD) total plasma TG of 3.31+/-0.93 mM; total C, 5.75+/-0.89 mM; HDL-C, 0.71+/-0.09 mM; and low-density lipoprotein (LDL)-C, 3.40+/-0.68 mM. Compared with placebo, fenofibrate reduced fasting TG levels by 36%, and triglyceride-rich lipoprotein (TRL, d<1.006 g/ml) -TG, and TRL-C levels by approximately 40%. In the postprandial state, fenofibrate reduced total TG, TRL-TG, TRL-C, TRL-apoC-III, and TRL-apoE levels by -35% (all values of p<0.01). Fasted and fed HDL-C and apoA-I levels were increased -10%, and total cholesterol/HDL cholesterol ratios were decreased -15% by fenofibrate. No significant differences were observed in mean LDL-C and LDL-apoB levels. A 6% increase in the LDL-C/LDL-apoB ratio during fenofibrate treatment indicated a shift to larger, more buoyant LDL particles. A small, but statistically significant (p<0.01) increase was observed in fasted and fed Lp(a) levels during fenofibrate treatment. Hemostatic parameters were not significantly affected by fenofibrate, except for a 12-15% decrease (p<0.05) in fibrinogen levels in the fasted and fed state, and a significant increase (43%; p<0.05) in fasting levels of plasminogen activator-inhibitor-1. These data demonstrate that micronized fenofibrate is highly effective, in both the fed and fasted state, in reducing TRL lipids and apolipoproteins, and in reducing plasma fibrinogen levels of men with an atherogenic lipoprotein profile. |
| Effect of minor illness on serum cholesterol level Hyman, D. J., D. C. Barrett, et al. (1992), Am J Prev Med 8(2): 100-3. Abstract: To ascertain the impact of minor illness on total plasma cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), we analyzed data collected on 6,880 persons examined for the Stanford Five-City Project. Overall, 8.4% of the population reported having a minor illness on the day of examination, although there were substantial variations in minor illness rates with season, city, and year of data collection. After adjustment for age, sex, body mass index, season, and city of residence, we found that those who reported minor illness at the time of examination had a lower mean TC than those who were well (195.9 mg/dL versus 201.2 mg/dL, P less than.005). HDL-C was 51.2 mg/dL in persons with minor illness, and 52.3 mg/dL in persons without (P =.13). Dietary recall data covering the 24-hour period before the examination was available on a subset of the patients. No dietary differences appeared between individuals who reported minor illness and those who did not. In a subset of 162 persons with a minor illness who were followed longitudinally for up to six years, TC adjusted for age was 191.8 mg/dL with minor illness and 196.1 mg/dL without, a difference that was not statistically significant. The results of this study imply that minor illness may contribute to some of the biological variability of TC and HDL-C. Although small, a differential rate of minor illness may sometimes significantly affect interpretation of TC epidemiological and intervention studies or the timing of measurements in clinical practice. |
| Effect of moderate alcohol consumption on parameters of reverse cholesterol transport in postmenopausal women Sierksma, A., S. H. Vermunt, et al. (2004), Alcohol Clin Exp Res 28(4): 662-6. Abstract: BACKGROUND: Alcohol consumption is associated with increased high-density lipoprotein (HDL) cholesterol levels. One of the main antiatherogenic functions of HDL is reverse cholesterol transport. Three early steps of reverse cholesterol transport are (1) cellular cholesterol efflux, (2) plasma cholesterol esterification (EST), and (3) cholesteryl ester transfer (CET) to apolipoprotein B-containing lipoproteins. Our previous study in healthy middle-aged men showed that moderate alcohol consumption increases cellular cholesterol efflux and EST. This study investigated the effect of moderate alcohol consumption on three early steps of reverse cholesterol transport in postmenopausal women. METHODS: In a randomized crossover study, 18 postmenopausal women--all apparently healthy, non-smoking, and moderate alcohol drinkers--consumed white wine or white grape juice with evening dinner during 2 successive periods of 3 weeks. During the white wine period, alcohol intake equaled 24 g/day. At the end of each of the two experimental periods, blood samples were collected. RESULTS: Three weeks of alcohol consumption increased serum HDL cholesterol levels (5.0%; p < 0.05), serum HDL phospholipid levels (5.8%; p < 0.05), and the ex vivo cellular cholesterol efflux capacity of plasma, measured with Fu5AH cells (3.4%; p < 0.05). Plasma EST and CET did not change. CONCLUSIONS: Moderate alcohol intake increases serum HDL cholesterol level and stimulates cellular cholesterol efflux in postmenopausal women. Moderate alcohol consumption does not seem to affect two other early steps of reverse cholesterol transport at this level of alcohol intake. Our data suggest that the relative protection of moderate alcohol consumption against cardiovascular disease in postmenopausal women may involve the stimulation of reverse cholesterol transport through increased HDL. |